Gripper pusher mechanism for tissue apposition systems

ABSTRACT

The invention provides devices, systems and methods for tissue approximation and repair at treatment sites. The devices, systems and methods of the invention will find use in a variety of therapeutic procedures, including endovascular, minimally-invasive, and open surgical procedures, and can be used in various anatomical regions, including the abdomen, thorax, cardiovascular system, heart, intestinal tract, stomach, urinary tract, bladder, lung, and other organs, vessels, and tissues. The invention is particularly useful in those procedures requiring minimally-invasive or endovascular access to remote tissue locations, where the instruments utilized must negotiate long, narrow, and tortuous pathways to the treatment site. In addition, many of the devices and systems of the invention are adapted to be reversible and removable from the patient at any point without interference with or trauma to internal tissues.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to medical methods, devices, andsystems. In particular, the present invention relates to methods,devices, and systems for the endovascular, percutaneous or minimallyinvasive surgical treatment of bodily tissues, such as tissueapproximation or valve repair. More particularly, the present inventionrelates to repair of valves of the heart and venous valves.

Surgical repair of bodily tissues often involves tissue approximationand fastening of such tissues in the approximated arrangement. Whenrepairing valves, tissue approximation includes coapting the leaflets ofthe valves in a therapeutic arrangement which may then be maintained byfastening or fixing the leaflets. Such coaptation can be used to treatregurgitation which most commonly occurs in the mitral valve.

Mitral valve regurgitation is characterized by retrograde flow from theleft ventricle of a heart through an incompetent mitral valve into theleft atrium. During a normal cycle of heart contraction (systole), themitral valve acts as a check valve to prevent flow of oxygenated bloodback into the left atrium. In this way, the oxygenated blood is pumpedinto the aorta through the aortic valve. Regurgitation of the valve cansignificantly decrease the pumping efficiency of the heart, placing thepatient at risk of severe, progressive heart failure.

Mitral valve regurgitation can result from a number of differentmechanical defects in the mitral valve or the left ventricular wall. Thevalve leaflets, the valve chordae which connect the leaflets to thepapillary muscles, the papillary muscles or the left ventricular wallmay be damaged or otherwise dysfunctional. Commonly, the valve annulusmay be damaged, dilated, or weakened limiting the ability of the mitralvalve to close adequately against the high pressures of the leftventricle.

The most common treatments for mitral valve regurgitation rely on valvereplacement or repair including leaflet and annulus remodeling, thelatter generally referred to as valve annuloplasty. A recent techniquefor mitral valve repair which relies on suturing adjacent segments ofthe opposed valve leaflets together is referred to as the “bow-tie” or“edge-to-edge” technique. While all these techniques can be veryeffective, they usually rely on open heart surgery where the patient'schest is opened, typically via a sternotomy, and the patient placed oncardiopulmonary bypass. The need to both open the chest and place thepatient on bypass is traumatic and has associated high mortality andmorbidity. More recently, minimially invasive catheter based procedureshave been developed to deliver implantable clips to the incompetentvalve. These clips are used to fasten a portion of the valve leafletstogether, thereby reducing the regurgitation. While the clips appear tobe promising, delivery and deployment of the clip can be challenging. Insome situations, it may be challenging to visualize the clip and valveleaflets using techniques such as fluoroscopy and echocardiography.Therefore, improved attachment mechanisms and attachment evaluationmethods would be desirable.

For these reasons, it would be desirable to provide improved methods,devices, and systems for performing the repair of mitral and othercardiac valves. Such methods, devices, and systems should preferably notrequire open chest access and be capable of being performed eitherendovascularly, i.e., using devices which are advanced to the heart froma point in the patient's vasculature remote from the heart or by aminimally invasive approach. Further, such devices and systems shouldprovide features which allow easier delivery of fixation devices, aswell as repositioning and optional removal of the fixation device priorto fixation to ensure optimal placement. Still more preferably, themethods, devices, and systems would be useful for repair of tissues inthe body other than heart valves. At least some of these objectives willbe met by the inventions described hereinbelow.

2. Description of the Background Art

Minimally invasive and percutaneous techniques for coapting andmodifying mitral valve leaflets to treat mitral valve regurgitation aredescribed in PCT Publication Nos. WO 98/35638; WO 99/00059; WO 99/01377;and WO 00/03759.

Maisano et al. (1998) Eur. J. Cardiothorac. Surg. 13:240-246; Fucci etal. (1995) Eur. J. Cardiothorac. Surg. 9:621-627; and Umana et al.(1998) Ann. Thorac. Surg. 66:1640-1646, describe open surgicalprocedures for performing “edge-to-edge” or “bow-tie” mitral valverepair where edges of the opposed valve leaflets are sutured together tolessen regurgitation. Dec and Fuster (1994) N. Engl. J. Med.331:1564-1575 and Alvarez et al. (1996) J. Thorac. Cardiovasc. Surg.112:238-247 are review articles discussing the nature of and treatmentsfor dilated cardiomyopathy.

Mitral valve annuloplasty is described in the following publications.Bach and Bolling (1996) Am. J. Cardiol. 78:966-969; Kameda et al. (1996)Ann. Thorac. Surg. 61:1829-1832; Bach and Bolling (1995) Am. Heart J.129:1165-1170; and Bolling et al. (1995) 109:676-683. Linear segmentalannuloplasty for mitral valve repair is described in Ricchi et al.(1997) Ann. Thorac. Surg. 63:1805-1806. Tricuspid valve annuloplasty isdescribed in McCarthy and Cosgrove (1997) Ann. Thorac. Surg. 64:267-268;Tager et al. (1998) Am. J. Cardiol. 81:1013-1016; and Abe et al. (1989)Ann. Thorac. Surg. 48:670-676.

Percutaneous transluminal cardiac repair procedures are described inPark et al. (1978) Circulation 58:600-608; Uchida et al. (1991) Am.Heart J. 121: 1221-1224; and Ali Khan et al. (1991) Cathet. Cardiovasc.Diagn. 23:257-262.

Endovascular cardiac valve replacement is described in U.S. Pat. Nos.5,840,081; 5,411,552; 5,554,185; 5,332,402; 4,994,077; and 4,056,854.See also U.S. Pat. No. 3,671,979 which describes a catheter fortemporary placement of an artificial heart valve.

Other percutaneous and endovascular cardiac repair procedures aredescribed in U.S. Pat. Nos. 4,917,089; 4,484,579; and 3,874,338; and PCTPublication No. WO 91/01689.

Thoracoscopic and other minimally invasive heart valve repair andreplacement procedures are described in U.S. Pat. Nos. 5,855,614;5,829,447; 5,823,956; 5,797,960; 5,769,812; and 5,718,725.

BRIEF SUMMARY OF THE INVENTION

The invention provides devices, systems and methods for tissueapproximation and repair at treatment sites. The devices, systems andmethods of the invention will find use in a variety of therapeuticprocedures, including endovascular, minimally-invasive, and opensurgical procedures, and can be used in various anatomical regions,including the abdomen, thorax, cardiovascular system, heart, intestinaltract, stomach, urinary tract, bladder, lung, and other organs, vessels,and tissues. The invention is particularly useful in those proceduresrequiring minimally-invasive or endovascular access to remote tissuelocations, where the instruments utilized must negotiate long, narrow,and tortuous pathways to the treatment site. In addition, many of thedevices and systems of the invention are adapted to be reversible andremovable from the patient at any point without interference with ortrauma to internal tissues.

In preferred embodiments, the devices, systems and methods of theinvention are adapted for fixation of tissue at a treatment site.Exemplary tissue fixation applications include cardiac valve repair,septal defect repair, vascular ligation and clamping, laceration repairand wound closure, but the invention may find use in a wide variety oftissue approximation and repair procedures. In a particularly preferredembodiment, the devices, systems and methods of the invention areadapted for repair of cardiac valves, and particularly the mitral valve,as a therapy for regurgitation. The invention enables two or more valveleaflets to be coapted using an “edge-to-edge” or “bow-tie” technique toreduce regurgitation, yet does not require open surgery through thechest and heart wall as in conventional approaches. Using the devices,systems and methods of the invention, the mitral valve can be accessedfrom a remote surgical or vascular access point and the two valveleaflets may be coapted using endovascular or minimally invasiveapproaches. While less preferred, in some circumstances the inventionmay also find application in open surgical approaches as well. Accordingto the invention, the mitral valve may be approached either from theatrial side (antegrade approach) or the ventricular side (retrogradeapproach), and either through blood vessels or through the heart wall.

The devices, systems and methods of the invention are centered onvariety of devices which may be used individually or in a variety ofcombinations to form interventional systems. In preferred embodiments,the interventional system includes a multi-catheter guiding system, adelivery catheter and an interventional device. Each of these componentswill be discussed herein.

In a first aspect of the present invention, a system for fixing tissuecomprises an implantable tissue fixation device comprising a pair offixation elements each having a first end, a free end opposite the firstend, and an engagement surface therebetween for engaging the tissue. Thefixation device further comprises a pair of gripping elements. Eachgripping element is moveable with respect to one of the fixationelements and is disposed in opposition to one of the engagement surfacesso as to capture tissue therebetween. The system also comprises agripper pusher releasably coupled to the implantable fixation deviceadjacent the pair of gripping elements. The gripper pusher has anexpanded configuration and a collapsed configuration. In the expandedconfiguration the gripper pusher engages the pair of gripping elementsand advances the pair of gripping elements toward the engagementsurfaces of the fixation elements. In the collapsed configuration thegripper pusher has a reduced radial profile relative to the gripperpusher radial profile in the expanded configuration thereby allowing thepair of gripping elements to move away from the engagement surfaces ofthe fixation elements.

The first ends of the fixation elements may be movably coupled togethersuch that the fixation elements are moveable between a closed positionand an inverted position. In the closed position, the engagementsurfaces may face each other, and in the inverted position theengagement surfaces may face away from each other. Each fixation elementmay be at least partially concave such that each gripping element isseparated from an opposing engagement surface in an undeployedconfiguration, and each gripping element may be at least partiallyrecessed within a fixation element in a deployed configuration. Thefixation elements may be further moveable to an open position betweenthe closed position and the inverted position.

The gripping elements may be movable independently of the fixationelements. They may be biased toward the engagement surfaces. Thegripping elements may be approximately parallel to each other in anundeployed configuration.

The gripper pusher may comprise a spring element that moves from thecollapsed configuration to the expanded configuration when a compressiveforce is applied thereto.

The spring element may comprise a longitudinal axis, and the compressiveforce may be applied in a direction substantially parallel thereto. Thespring element may be resiliently biased to return to the collapsedconfiguration when the compressive force is released. The spring elementmay be resiliently biased to return to the expanded configuration. Thegripper pusher may comprise two spring elements, or an elongatedeflectable arm. The arm may comprise a plurality of peaks or bowedregions. The deflectable arm may be biased to return to the expandedconfiguration, and proximal retraction of the proximal elements maycollapse the deflectable arm from the expanded configuration to thecollapsed configuration.

The gripper pusher may comprise an attachment mechanism for releasablyattaching a distal portion of the gripper pusher to the implantablefixation device. The attachment mechanism may comprise a notched regionon a distal portion of the gripper pusher, and a boss adjacent aproximal end of the implantable fixation device. The notched region maybe sized to accept the boss. The system may further comprise an elongatedelivery shaft having a proximal portion and a distal portion. Thedistal portion of the elongate delivery shaft may be releasably coupledto a proximal portion of the gripper pusher. The gripper pusher maycomprise an attachment ring or coupling ring that may be coupled to theproximal portion thereof, and the attachment ring may be slidablydisposed over the delivery shaft.

The system may further comprise an actuation mechanism that may becoupled to the fixation elements, and that is adapted to move thefixation elements between the closed position and the inverted position.The system may also comprise a coupling member for detachably couplingthe fixation device to an elongate delivery shaft. A covering may bedisposed on the fixation elements that is adapted to promote tissueingrowth. A coating may be disposed on the fixation elements that isadapted to deliver a therapeutic agent to the treatment tissue.

In another aspect of the invention, a system for fixing tissue maycomprise an implantable tissue fixation device and a first gripperactuator. The implantable tissue fixation device comprises a pair offixation elements and a pair of gripping elements. The pair of fixationelements comprises a first fixation element and a second fixationelement. Each fixation element has a first end, a free end opposite thefirst end, and an engagement surface therebetween for engaging thetissue. The pair of gripping elements comprises a first gripping elementand a second gripping element. The first gripping element is moveablewith respect to the first fixation element. The first gripping elementis also disposed in opposition to the engagement surface of the firstfixation element so as to capture tissue therebetween. Similarly, thesecond gripping element is moveable with respect to the second fixationelement and is disposed in opposition to the engagement surface of thesecond fixation element so as to capture tissue therebetween. The firstgripper actuator is releaseably coupled to the implantable fixationdevice adjacent to the first gripping element. The first gripperactuator has a first configuration and a second configuration. Actuatingthe first gripper actuator between the first configuration and thesecond configuration moves the first gripping element with respect tothe first fixation element. Typically, the system further comprises asecond gripper actuator. The second gripper actuator is releaseablycoupled to the implantable fixation device adjacent to the secondgripping element. The second gripper actuator similarly has a firstconfiguration and a second configuration. Actuating the second gripperactuator between the first configuration and the second configurationmoves the second gripping element with respect to the second fixationelement. The first gripper actuator and the second gripper actuator areactuatable between their first configurations and their secondconfigurations independently of each other.

In many embodiments, the first ends are movably coupled together suchthat the fixation elements are moveable between a closed position and aninverted position. In the closed position, the first ends of the pair offixation elements have their engagement surfaces facing each other. Inthe open position, the first ends of the pair of fixation elements havetheir engagement surfaces facing away from each other. The system mayfurther comprise an actuation mechanism coupled to the fixationelements. The actuation mechanism is adapted to move the fixationelements between the closed position and the inverted position.

In many embodiments, each fixation element is at least partiallyconcave. By being at least partially concave, each gripping element isseparated from an opposing engagement surface in an undeployedconfiguration and may be at least partially recessed within the fixationelement in a deployed configuration. The fixation elements may furtherbe moveable to an open position between the closed position and theinverted position.

In addition to being independently moveable relative to one another, thegripping elements may be movable independently of the fixation elements.The gripping elements may be biased toward the engagement surfaces. Thegripping elements may be approximately parallel to each other in anundeployed configuration.

In many embodiments, the system further comprises a gripper pusher asdescribed above. The gripper pusher is releasably coupled to theimplantable fixation device adjacent the pair of gripping elements. Thegripper pusher has an expanded configuration and a collapsedconfiguration. In the expanded configuration, the gripper pusher engagesone or more of the pair of gripping elements and advances one or more ofthe pair of gripping elements toward the engagement surfaces of thefixation elements. In the collapsed configuration, the gripper pusherhas a reduced radial profile relative to the gripper pusher radialprofile in the expanded configuration. This reduced radial profileallows the pair of gripping elements to move away from the engagementsurfaces of the fixation elements.

In many embodiments, the first gripper actuator comprises a first wireand the second gripper actuator comprises a second wire. The first wireand the second wire may be substantially flat or have other profilessuch as round, square, elliptical, etc. Preferably, the substantiallyflat sides of the first and second wire are positioned to engage thefirst and second gripping elements and are biased to bend or flex alongthe flat side. Thus, as the first and second wires are advanced, theywill tend to deflect in the direction toward the first and secondgripping elements.

In many embodiments, at least one of a distal end of the first gripperactuator or a distal end of the second gripper actuator is releaseablycoupled to the implantation fixation device by a suture knot.

In many embodiments, the system further comprises an elongate deliveryshaft having a proximal portion and a distal portion. The distal portionof the elongate delivery shaft is releasably coupled to a proximalportion of the fixation device. Each of the first and second gripperactuators may comprise distal portions. The distal portions of the firstand second gripper actuators may be releasably coupled to at least oneof the distal portion of the elongate delivery shaft or the proximalportion of the fixation device. For example, the distal portions of thefirst gripper actuator and second gripper actuator may each comprise aclosed loop or a coiled distal end disposed over at least one of thedistal portion of the elongate delivery shaft or the proximal portion ofthe fixation device.

In many embodiments, the proximal portion of the fixation devicecomprises a channel having a pair of notches. The distal portion of theelongate delivery shaft comprises a pair of L-shaped ends resilientlybiased to fit into the pair of notches. The distal portion of theelongate delivery shaft is releasably coupled to the proximal portion ofthe fixation device by placing the pair of L-shaped ends into channel ofthe fixation device and locking the pair of notches in the channel. Thefirst and second gripper actuators each comprise distal ends. Placingthe distal ends of the first and second gripper actuators and couplingthe distal portion of the elongate delivery shaft to the proximalportion of the fixation device locks the distal ends of the first andsecond gripper actuators in place. The first and second gripper actuatormay each comprise T-shaped distal ends. The system may further comprisea covering assembly coupled to and disposed over the distal portion ofthe elongate delivery shaft. The covering assembly comprises an outerslideable section and an inner section having a pair of T-shapedopenings. The first and second gripper actuator are releaseably coupledto the fixation device by sliding the T-shaped distal ends of the firstand second gripper actuators into the pair of the T-shaped opening ofthe inner section of the covering assembly and sliding the outerslideable section to cover the T-shaped openings.

In many embodiments, the first and second gripper actuators arereleaseably coupled to the first and second gripping elements,respectively. The first and second gripping elements may each compriseportions extending radially outward. The system may further comprisefirst and second holding elements. The first holding element is coupledto the first gripper actuator and releaseably coupled to the firstgripping element at its portion extending radially outward. The secondholding element is coupled to the second gripper actuator andreleaseably coupled to the second gripping element at its portionextending radially outward. The first and second holding element maycomprises a first and second ring, respectively. The rings are disposedover the portions extending radially outward of their respectivegripping elements. Alternatively, the first and second holding elementsmay comprise a first and second clip, respectively. The clips arereleaseably attached to the portion extending radially outward of theirrespective gripping elements. The first and second clips may eachcomprise a pair of legs disposed over the length of their respectivegripping elements. The portions extending radially outward of the firstand second gripping elements may each have apertures. The first andsecond gripper actuators may be threaded through the apertures of theradially outward portion of the first and second gripping elements,respectively. The first and second gripper actuators may each comprisean enlarged portion. The diameters of the enlarged portions of the firstand second gripper actuator may be greater than that of the aperture ofthe portion extending radially outward of the first and second grippingelements, respectively, to facilitate moving the first and secondgripping elements. The enlarged portions of the first and second gripperactuator may comprises a sleeve disposed over the first and secondgripper actuators.

In many embodiments, the first and second gripper actuator and thesecond gripper actuator each comprise an actuation line and a releaseline. Each actuation line may comprise a loop while each release linemay comprises a single release cable. The single release cable isthreaded through the loop of the actuation line when a gripper actuatoris coupled a gripping element. Pulling the single release cable outthrough the loop of the actuation line allows a gripper actuator to bereleased from a gripping element.

The system may further comprise a coupling member for detachablycoupling the fixation device to an elongate delivery shaft, a coveringon the fixation elements adapted for promoting tissue growth, and/or acoating on the fixation elements adapted for delivering a therapeuticagent.

Another aspect of the invention provides a method for fixing tissue. Animplantable tissue fixation device is provided. The fixation devicecomprises a pair of fixation elements. Each fixation element has a firstend, a free end opposite the first end, and an engagement surfacetherebetween for engaging the tissue. The fixation device furthercomprises a pair of gripping elements. Each gripping element is moveablewith respect to one of the fixation elements and is disposed inapposition to one of the engagement surfaces so as to capture tissuetherebetween. The fixation element is positioned relative to tissue sothat the tissue is disposed between the pair of gripping elements andthe engagement surfaces of the pair of fixation element. The pair ofgripping elements is advanced toward the engagement surfaces of thefixation elements.

In many embodiments, a gripper pusher releasably coupled to theimplantable fixation device adjacent the pair of gripping elements isprovided, and the pair of gripping elements is advanced toward theengagement surfaces of the fixation elements by engaging the pair ofgripping elements with the gripper pusher. Engaging the pair of grippingelements with the gripper pusher may comprise placing the gripper pusherinto an expanded configuration from a collapsed configuration. Thegripper pusher may comprise a spring element having a longitudinal axis,and the pair of gripping elements may be engaged with the gripper pusherby applying a compressive force to the spring element in a directionsubstantially parallel to the longitudinal axis to move the gripperpusher to the expanded configuration. The gripper pusher may be placedinto the collapsed configuration from the expanded configuration toreduce the radial profile of the gripper pusher relative to the gripperpusher radial profile in the expanded configuration to allow the pair ofgripping elements to move away from the engagement surfaces of thefixation elements.

In many embodiments, the first ends of the pair of the fixation elementsis moved between a closed position to an inverted position. Theengagement surfaces face each other when the fixation element is in theclosed position and away from each other when the fixation element is inthe inverted position. The fixation elements may be moved to an openposition between the closed position and the inverted position.

Another aspect of the invention provides a method of fixing tissue. Animplantable tissue fixation device is provided. The fixation devicecomprises a pair of fixation elements, which comprises a first fixationelement and a second fixation element. Each fixation element has a firstend, a free end opposite the first end, and an engagement surfacetherebetween for engaging the tissue. The fixation device furthercomprises a pair of gripping elements, which comprise a first grippingelement and a second gripping element. The first gripping element isdisposed in apposition to the engagement surface of the first fixationelement. The second gripping element is likewise disposed in appositionto the engagement surface of the second fixation element. The fixationelement is positioned relative to tissue so that the tissue is disposedbetween the first gripping element and the engagement surface of thefirst fixation element. The tissue is captured between the firstgripping element and the engagement surface of the first fixationelement by moving the first gripping element with respect to the firstfixation element. The position of the second gripping element ismaintained with respect to the second fixation element while the firstgripping element is moved with respect to the first fixation element.

In many embodiments, a first gripping element actuator coupled to thefirst gripping element and a second gripping element actuator coupled tothe second gripping element are provided. The tissue between the firstgripping element and the engagement surface of the first fixationelement may be captured by moving the first gripping element actuator tomove the first gripping element. The position of the second grippingelement with respect to the second fixation element may be maintained byholding the second gripping element actuator stationary relative to thesecond gripping element.

In many embodiments, the captured tissue between the first grippingelement and the engagement surface of the first fixation element isreleased by moving the first gripping element away from the firstfixation element. The fixation can then be repositioned relative to thetissue.

In many embodiments, the fixation element is positioned relative totissue so that the tissue is disposed between the second grippingelement and the engagement surface of the second fixation element. Thetissue between the second gripping element and the engagement surface ofthe second fixation element may be captured by moving the secondgripping element with respect to the second fixation element. In someembodiments, the captured tissue between the pair of gripping elementsand the engagement surfaces of the pair of fixation elements can bereleased by moving the pair of gripping elements away from theengagement surfaces of the pair of fixation elements. The fixation canthen be repositioned relative to the tissue.

Other aspects of the nature and advantages of the invention are setforth in the detailed description set forth below, taken in conjunctionwith the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates the left ventricle and left atrium of the heartduring systole.

FIG. 2A illustrates free edges of leaflets in normal coaptation, andFIG. 2B illustrates the free edges in regurgitative coaptation.

FIGS. 3A-3C illustrate grasping of the leaflets with a fixation device,inversion of the distal elements of the fixation device and removal ofthe fixation device, respectively.

FIG. 4 illustrates the position of the fixation device in a desiredorientation relative to the leaflets.

FIGS. 5A-5B and 6A-6B illustrate exemplary embodiments of couplingmechanisms of the instant application.

FIG. 7 illustrates an embodiment of the fixation device of the presentinvention.

FIGS. 8A-8B, 9A-9B, 10A-10B, 11A-11B, and 12-14 illustrate the fixationdevice of FIG. 7 in various possible positions during introduction andplacement of the device within the body to perform a therapeuticprocedure.

FIGS. 15A-15H illustrate the fixation device of FIG. 7 with a gripperpusher.

FIGS. 15I-15V illustrate the fixation device of FIG. 7 withindependently actuatable proximal elements.

FIGS. 15W1-15AB7 illustrate various embodiments of coupling a proximalelement line to a proximal element of the fixation device of FIG. 7.

FIGS. 15AC1-15AC4 illustrate various control mechanisms of theindependently actuatable proximal element lines of the fixation deviceof FIGS. 15I-15V.

FIGS. 16A-16C illustrate a covering on the fixation device wherein thedevice is in various positions.

FIG. 17 illustrates an embodiment of the fixation device includingproximal elements and a locking mechanism.

FIG. 18 provides a cross-sectional view of the locking mechanism of FIG.17.

FIGS. 19-20 provide a cross-sectional view of the locking mechanism inthe unlocked and locked positions respectively.

FIGS. 21 and 22A-22B illustrate another embodiment of a lockingmechanism.

FIGS. 23 and 24A-24B illustrate yet another embodiment of a lockingmechanism.

FIG. 25 is a perspective view of an embodiment of a delivery catheterfor a fixation device.

FIG. 26 illustrates an embodiment of a fixation device coupled to thedistal end of a delivery catheter.

FIG. 27 illustrates a portion of the shaft of a delivery catheter and afixation device which is coupleable with the catheter.

FIGS. 28A-28B illustrate an exemplary embodiment of an actuator rodassembly.

FIGS. 29A-28B, 30A-30B, 31A-31B, and 32A-32B illustrate layers of anexemplary cable used in the actuator rod of FIGS. 28A-28B.

FIGS. 33A-33B, 34A-34B, 35A-35B, 36A-36B, and 37A-37B illustrate layersin another exemplary cable used in the actuator rod of FIGS. 28A-28B.

FIGS. 38-40 are cross-sectional views of embodiments of the shaft of thedelivery catheter.

FIGS. 40A-40B illustrate embodiments of the nose of the shaft of thedelivery catheter.

FIG. 41A-41C illustrate various arrangements of lock lines engagingrelease harnesses of a locking mechanism.

FIGS. 42A-42B illustrate various arrangements of proximal element linesengaging proximal elements of a fixation device.

FIG. 43 illustrates an embodiment of the handle of the deliverycatheter.

FIG. 44 is a cross-sectional view of the main body of the handle.

FIG. 45 illustrates an embodiment of a lock line handle.

FIG. 45A illustrates the lock line handle of FIG. 45 positioned within asemi-tube which is disposed within the sealed chamber.

FIGS. 46A-46B illustrate a mechanism for applying tension to lock lines.

FIGS. 47 and 47A-47B illustrate features of the actuator rod control andhandle.

FIG. 48 is a perspective view of an embodiment of a multi-catheterguiding system of the present invention, and an interventional catheterpositioned therethrough.

FIG. 49A illustrates a primary curvature in an outer guide catheter.

FIG. 49B illustrates a secondary curvature in an inner guide catheter.

FIGS. 49C-49D illustrate example movement of an inner guide catheterthrough angle thetas.

FIG. 50A is a perspective side view of a multi-catheter guiding systemhaving an additional curve in the outer guide catheter.

FIG. 50B illustrates lifting of the outer guide catheter due to theadditional curve of FIG. 49A.

FIGS. 51A-51D illustrate a method of using the multi-catheter guidingsystem for accessing the mitral valve.

FIGS. 52A-52D illustrate curvature of a guide catheter of the presentinvention by the actuation of one or more pullwires.

FIG. 52E illustrates attachment of a pullwire to a tip ring.

FIGS. 53A-53I illustrate embodiments of the present invention comprisingsections constructed with the inclusion of braiding or a coil.

FIGS. 54A-54C illustrate a keying feature of the present invention.

FIGS. 55A-55B are perspective views of a guide catheter including aseries of articulating members.

FIG. 56 illustrates embodiments of the handles.

FIG. 57 illustrates the handles of FIG. 56 with a portion of the housingremoved.

FIG. 58 illustrates steering mechanisms within a handle.

FIG. 59 illustrates attachment of a pullwire to a disk.

FIGS. 60A-60B illustrate a hard stop peg restricting rotation of a disk.

FIGS. 61A-61C illustrates a portion of a hard stop gear assembly.

FIGS. 62A-62F illustrate a ball restricting rotation of a disk.

FIG. 63 illustrates an embodiment of a friction assembly.

FIG. 64 illustrates an embodiment of an interventional system of thepresent invention.

FIG. 64A illustrates an embodiment of a hemostatic valve for use withthe present invention.

FIG. 64B illustrates an embodiment of a fixation device introducer.

FIG. 65 illustrates another embodiment of an interventional system ofthe present invention.

FIGS. 66-68 illustrate an embodiment of a stabilizer base for use withthe present invention.

FIG. 69 illustrates a kit constructed in accordance with the principlesof the present invention.

FIG. 70 illustrates a handle in accordance with an exemplary embodiment.

DETAILED DESCRIPTION OF THE INVENTION I. Cardiac Physiology

The left ventricle LV of a normal heart H in systole is illustrated inFIG. 1. The left ventricle LV is contracting and blood flows outwardlythrough the tricuspid (aortic) valve AV in the direction of the arrows.Back flow of blood or “regurgitation” through the mitral valve MV isprevented since the mitral valve is configured as a “check valve” whichprevents back flow when pressure in the left ventricle is higher thanthat in the left atrium LA. The mitral valve MV comprises a pair ofleaflets having free edges FE which meet evenly to close, as illustratedin FIG. 1. The opposite ends of the leaflets LF are attached to thesurrounding heart structure along an annular region referred to as theannulus AN. The free edges FE of the leaflets LF are secured to thelower portions of the left ventricle LV through chordae tendinae CT(referred to hereinafter as the chordae) which include a plurality ofbranching tendons secured over the lower surfaces of each of the valveleaflets LF. The chordae CT in turn, are attached to the papillarymuscles PM which extend upwardly from the lower portions of the leftventricle and intraventricular septum IVS.

A number of structural defects in the heart can cause mitral valveregurgitation. Regurgitation occurs when the valve leaflets do not closeproperly allowing leakage from the ventricle into the atrium. As shownin FIG. 2A, the free edges of the anterior and posterior leafletsnormally meet along a line of coaptation C. An example of a defectcausing regurgitation is shown in FIG. 2B. Here an enlargement of theheart causes the mitral annulus to become enlarged, making it impossiblefor the free edges FE to meet during systole. This results in a gap Gwhich allows blood to leak through the valve during ventricular systole.Ruptured or elongated chordae can also cause a valve leaflet to prolapsesince inadequate tension is transmitted to the leaflet via the chordae.While the other leaflet maintains a normal profile, the two valveleaflets do not properly meet and leakage from the left ventricle intothe left atrium will occur. Such regurgitation can also occur inpatients who have suffered ischemic heart disease where the leftventricle does not contract sufficiently to effect proper closure.

II. General Overview

The present invention provides methods and devices for grasping,approximating and fixating tissues such as valve leaflets to treatcardiac valve regurgitation, particularly mitral valve regurgitation.The present invention also provides features that allow repositioningand removal of the device if so desired, particularly in areas whereremoval may be hindered by anatomical features such as chordae CT. Suchremoval would allow the surgeon to reapproach the valve in a new mannerif so desired.

Grasping will preferably be atraumatic providing a number of benefits.By atraumatic, it is meant that the devices and methods of the inventionmay be applied to the valve leaflets and then removed without causingany significant clinical impairment of leaflet structure or function.The leaflets and valve continue to function substantially the same asbefore the invention was applied. Thus, some minor penetration ordenting of the leaflets may occur using the invention while stillmeeting the definition of “atraumatic.” This enables the devices of theinvention to be applied to a diseased valve and, if desired, removed orrepositioned without having negatively affected valve function. Inaddition, it will be understood that in some cases it may be necessaryor desirable to pierce or otherwise permanently affect the leafletsduring either grasping, fixing or both. In some of these cases, graspingand fixation may be accomplished by a single device. Although a numberof embodiments are provided to achieve these results, a general overviewof the basic features will be presented herein. Such features are notintended to limit the scope of the invention and are presented with theaim of providing a basis for descriptions of individual embodimentspresented later in the application.

The devices and methods of the invention rely upon the use of aninterventional tool that is positioned near a desired treatment site andused to grasp the target tissue. In endovascular applications, theinterventional tool is typically an interventional catheter. In surgicalapplications, the interventional tool is typically an interventionalinstrument. In preferred embodiments, fixation of the grasped tissue isaccomplished by maintaining grasping with a portion of theinterventional tool which is left behind as an implant. While theinvention may have a variety of applications for tissue approximationand fixation throughout the body, it is particularly well adapted forthe repair of valves, especially cardiac valves such as the mitralvalve. Referring to FIG. 3A, an interventional tool 10, having adelivery device, such as a shaft 12, and a fixation device 14, isillustrated having approached the mitral valve MV from the atrial sideand grasped the leaflets LF. The mitral valve may be accessed eithersurgically or by using endovascular techniques, and either by aretrograde approach through the ventricle or by an antegrade approachthrough the atrium, as described above. For illustration purposes, anantegrade approach is described.

The fixation device 14 is releasably attached to the shaft 12 of theinterventional tool 10 at its distal end. When describing the devices ofthe invention herein, “proximal” shall mean the direction toward the endof the device to be manipulated by the user outside the patient's body,and “distal” shall mean the direction toward the working end of thedevice that is positioned at the treatment site and away from the user.With respect to the mitral valve, proximal shall refer to the atrial orupstream side of the valve leaflets and distal shall refer to theventricular or downstream side of the valve leaflets.

The fixation device 14 typically comprises proximal elements 16 (orgripping elements) and distal elements 18 (or fixation elements) whichprotrude radially outward and are positionable on opposite sides of theleaflets LF as shown so as to capture or retain the leafletstherebetween. The proximal elements 16 are preferably comprised ofcobalt chromium, nitinol or stainless steel, and the distal elements 18are preferably comprised of cobalt chromium or stainless steel, howeverany suitable materials may be used. The fixation device 14 is coupleableto the shaft 12 by a coupling mechanism 17. The coupling mechanism 17allows the fixation device 14 to detach and be left behind as an implantto hold the leaflets together in the coapted position.

In some situations, it may be desired to reposition or remove thefixation device 14 after the proximal elements 16, distal elements 18,or both have been deployed to capture the leaflets LF. Suchrepositioning or removal may be desired for a variety of reasons, suchas to reapproach the valve in an attempt to achieve better valvefunction, more optimal positioning of the device 14 on the leaflets,better purchase on the leaflets, to detangle the device 14 fromsurrounding tissue such as chordae, to exchange the device 14 with onehaving a different design, or to abort the fixation procedure, to name afew. To facilitate repositioning or removal of the fixation device 14the distal elements 18 are releasable and optionally invertible to aconfiguration suitable for withdrawal of the device 14 from the valvewithout tangling or interfering with or damaging the chordae, leafletsor other tissue. FIG. 3B illustrates inversion wherein the distalelements 18 are moveable in the direction of arrows 40 to an invertedposition. Likewise, the proximal elements 16 may be raised, if desired.In the inverted position, the device 14 may be repositioned to a desiredorientation wherein the distal elements may then be reverted to agrasping position against the leaflets as in FIG. 3A. Alternatively, thefixation device 14 may be withdrawn (indicated by arrow 42) from theleaflets as shown in FIG. 3C. Such inversion reduces trauma to theleaflets and minimizes any entanglement of the device with surroundingtissues. Once the device 14 has been withdrawn through the valveleaflets, the proximal and distal elements may be moved to a closedposition or configuration suitable for removal from the body or forreinsertion through the mitral valve.

FIG. 3 illustrates the position of the fixation device 14 in a desiredorientation in relation to the leaflets LF. This is a short-axis view ofthe mitral valve MV from the atrial side, therefore, the proximalelements 16 are shown in solid line and the distal elements 18 are shownin dashed line. The proximal and distal elements 16, 18 are positionedto be substantially perpendicular to the line of coaptation C. Thedevice 14 may be moved roughly along the line of coaptation to thelocation of regurgitation. The leaflets LF are held in place so thatduring diastole, as shown in FIG. 4, the leaflets LF remain in positionbetween the elements 16, 18 surrounded by openings O which result fromthe diastolic pressure gradient. Advantageously, leaflets LF are coaptedsuch that their proximal or upstream surfaces are facing each other in avertical orientation, parallel to the direction of blood flow throughmitral valve MV. The upstream surfaces may be brought together so as tobe in contact with one another or may be held slightly apart, but willpreferably be maintained in the vertical orientation in which theupstream surfaces face each other at the point of coaptation. Thissimulates the double orifice geometry of a standard surgical bow-tierepair. Color Doppler echo will show if the regurgitation of the valvehas been reduced. If the resulting mitral flow pattern is satisfactory,the leaflets may be fixed together in this orientation. If the resultingcolor Doppler image shows insufficient improvement in mitralregurgitation, the interventional tool 10 may be repositioned. This maybe repeated until an optimal result is produced wherein the leaflets LFare held in place.

Once the leaflets are coapted in the desired arrangement, the fixationdevice 14 is then detached from the shaft 12 and left behind as animplant to hold the leaflets together in the coapted position. Asmentioned previously, the fixation device 14 is coupled to the shaft 12by a coupling mechanism 17. FIGS. 5A-5B, 6A-6B illustrate exemplaryembodiments of such coupling mechanisms. FIG. 5A shows an upper shaft 20and a detachable lower shaft 22 which are interlocked at a joining lineor mating surface 24. The mating surface 24 may have any shape orcurvature which will allow or facilitate interlocking and laterdetachment. A snuggly fitting outer sheath 26 is positioned over theshafts 20, 22 to cover the mating surface 24 as shown. FIG. 5Billustrates detachment of the lower shaft 22 from the upper shaft 20.This is achieved by retracting the outer sheath 26, so that the matingsurface 24 is exposed, which allows the shafts 20, 22 to separate.

Similarly, FIG. 6A illustrates a tubular upper shaft 28 and a detachabletubular lower shaft 30 which are interlocked at a mating surface 32.Again, the mating surface 32 may have any shape or curvature which willallow or facilitate interlocking and later detachment. The tubular uppershaft 28 and tubular lower shaft 30 form an outer member having an axialchannel. A snuggly fitting rod 34 or inner member is inserted throughthe tubular shafts 28, to bridge the mating surface 32 as shown. The rod34 may also be used to actuate the fixation device, such as actuator rod64 seen in FIG. 26 or actuator rod 64 a illustrated in FIGS. 28A-28B,described below. FIG. 6B illustrates detachment of the lower shaft 30from the upper shaft 28. This is achieved by retracting the rod 34 to aposition above the mating surface 32 which in turn allows the shafts 28,30 to separate. Other examples of coupling mechanisms are described andillustrated in U.S. Pat. No. 6,752,813 (Attorney Docket No.020489-000400), and U.S. Patent Publication No. 2009/0163934 (AttorneyDocket No. 020489-001470US), the entire contents of each of which areincorporated herein by reference for all purposes.

In a preferred embodiment, mating surface 24 (or mating surface 32) is asigmoid curve defining a male element and female element on upper shaft20 (or upper shaft 28) which interlock respectively with correspondingfemale and male elements on lower shaft 22 (or lower shaft 30).Typically, the lower shaft is the coupling mechanism 17 of the fixationdevice 14. Therefore, the shape of the mating surface selected willpreferably provide at least some mating surfaces transverse to the axialaxis of the a mechanism 19 to facilitate application of compressive andtensile forces through the coupling mechanism 17 to the fixation device14, yet causing minimal interference when the fixation device 14 is tobe released from the upper shaft.

III. Fixation Device

A. Introduction and Placement of Fixation Device

The fixation device 14 is delivered to the valve or the desired tissueswith the use of a delivery device. The delivery device may be rigid orflexible depending on the application. For endovascular applications,the delivery device comprises a flexible delivery catheter which will bedescribed in later sections. Typically, however, such a cathetercomprises a shaft, having a proximal end and a distal end, and afixation device releasably attached to its distal end. The shaft isusually elongate and flexible, suitable for intravascular introduction.Alternatively, the delivery device may comprise a shorter and lessflexible interventional instrument which may be used for trans-thoracicsurgical introduction through the wall of the heart, although someflexibility and a minimal profile will generally be desirable. Afixation device is releasably coupleable with the delivery device asillustrated in FIG. 3A. The fixation device may have a variety of forms,a few embodiments of which will be described herein.

FIG. 7 illustrates another embodiment of a fixation device 14. Here, thefixation device 14 is shown coupled to a shaft 12 to form aninterventional tool 10. The fixation device 14 includes a couplingmember 19 and a pair of opposed distal elements 18. The distal elements18 comprise elongate arms 53, each arm having a proximal end 52rotatably connected to the coupling member 19 and a free end 54. Thefree ends 54 have a rounded shape to minimize interference with andtrauma to surrounding tissue structures. Preferably, each free end 54defines a curvature about two axes, one being an axis 66 perpendicularto longitudinal axis of arms 53. Thus, the engagement surfaces 50 have acupped or concave shape to surface area in contact with tissue and toassist in grasping and holding the valve leaflets. This further allowsarms 53 to nest around the shaft 12 in the closed position to minimizethe profile of the device. Preferably, arms 53 are at least partiallycupped or curved inwardly about their longitudinal axes 66. Also,preferably, each free end 54 defines a curvature about an axis 67perpendicular to axis 66 or the longitudinal axis of arms 53. Thiscurvature is a reverse curvature along the most distal portion of thefree end 54. Likewise, the longitudinal edges of the free ends 54 mayflare outwardly. Both the reverse curvature and flaring minimize traumato the tissue engaged therewith.

In a preferred embodiment suitable for mitral valve repair, thetransverse width across engagement surfaces 50 (which determines thewidth of tissue engaged) is at least about 2 mm, usually 3-10 mm, andpreferably about 4-6 mm. In some situations, a wider engagement isdesired wherein the engagement surfaces 50 are larger, for example about2 cm, or multiple fixation devices are used adjacent to each other. Arms53 and engagement surfaces 50 are configured to engage a length oftissue of about 4-10 mm, and preferably about 6-8 mm along thelongitudinal axis of arms 53. Arms 53 further include a plurality ofopenings to enhance grip and to promote tissue ingrowth followingimplantation.

The valve leaflets are grasped between the distal elements 18 andproximal elements 16. In some embodiments, the proximal elements 16 areflexible, resilient, and cantilevered from coupling member 19. Theproximal elements are preferably resiliently biased toward the distalelements. Each proximal element 16 is shaped and positioned to be atleast partially recessed within the concavity of the distal element 18when no tissue is present. When the fixation device 14 is in the openposition, the proximal elements 16 are shaped such that each proximalelement 16 is separated from the engagement surface 50 near the proximalend 52 of arm 53 and slopes toward the engagement surface 50 near thefree end 54 with the free end of the proximal element contactingengagement surface 50, as illustrated in FIG. 7. This shape of theproximal elements 16 accommodates valve leaflets or other tissues ofvarying thicknesses.

Proximal elements 16 include a plurality of openings 63 and scallopedside edges 61 to increase grip on tissue. The proximal elements 16optionally include frictional accessories, frictional features orgrip-enhancing elements to assist in grasping and/or holding theleaflets. In preferred embodiments, the frictional accessories comprisebarbs 60 having tapering pointed tips extending toward engagementsurfaces 50. It may be appreciated that any suitable frictionalaccessories may be used, such as prongs, windings, bands, barbs,grooves, channels, bumps, surface roughening, sintering, high-frictionpads, coverings, coatings or a combination of these. Optionally, magnetsmay be present in the proximal and/or distal elements. It may beappreciated that the mating surfaces will be made from or will includematerial of opposite magnetic charge to cause attraction by magneticforce. For example, the proximal elements and distal elements may eachinclude magnetic material of opposite charge so that tissue is heldunder constant compression between the proximal and distal elements tofacilitate faster healing and ingrowth of tissue. Also, the magneticforce may be used to draw the proximal elements 16 toward the distalelements 18, in addition to or alternatively to biasing of the proximalelements toward the distal elements. This may assist in deployment ofthe proximal elements 16. In another example, the distal elements 18each include magnetic material of opposite charge so that tissuepositioned between the distal elements 18 is held therebetween bymagnetic force. Actuation of the proximal elements may also beaccomplished using one or more proximal element lines or actuators suchas those described below.

The proximal elements 16 may be covered with a fabric or other flexiblematerial as described below to enhance grip and tissue ingrowthfollowing implantation. Preferably, when fabrics or coverings are usedin combination with barbs or other frictional features, such featureswill protrude through such fabric or other covering so as to contact anytissue engaged by proximal elements 16.

In an exemplary embodiment, proximal elements 16 are formed frommetallic sheet of a spring-like material using a stamping operationwhich creates openings 63, scalloped edges 61 and barbs 60.Alternatively, proximal elements 16 could be comprised of a spring-likematerial or molded from a biocompatible polymer. It should be noted thatwhile some types of frictional accessories that can be used in thepresent invention may permanently alter or cause some trauma to thetissue engaged thereby, in a preferred embodiment, the frictionalaccessories will be atraumatic and will not injure or otherwise affectthe tissue in a clinically significant way. For example, in the case ofbarbs 60, it has been demonstrated that following engagement of mitralvalve leaflets by fixation device 14, should the device later be removedduring the procedure barbs 60 leave no significant permanent scarring orother impairment of the leaflet tissue and are thus consideredatraumatic.

The fixation device 14 also includes an actuation mechanism 58. In thisembodiment, the actuation mechanism 58 comprises two link members orlegs 68, each leg 68 having a first end 70 which is rotatably joinedwith one of the distal elements 18 at a riveted joint 76 and a secondend 72 which is rotatably joined with a stud 74. The legs 68 arepreferably comprised of a rigid or semi-rigid metal or polymer such asElgiloy®, cobalt chromium or stainless steel, however any suitablematerial may be used. While in the embodiment illustrated both legs 68are pinned to stud 74 by a single rivet 78, it may be appreciated,however, that each leg 68 may be individually attached to the stud 74 bya separate rivet or pin. The stud 74 is joinable with an actuator rod 64(not shown) which extends through the shaft 12 and is axially extendableand retractable to move the stud 74 and therefore the legs 68 whichrotate the distal elements 18 between closed, open and invertedpositions. Likewise, immobilization of the stud 74 holds the legs 68 inplace and therefore holds the distal elements 18 in a desired position.The stud 74 may also be locked in place by a locking feature which willbe further described in later sections.

In any of the embodiments of fixation device 14 disclosed herein, it maybe desirable to provide some mobility or flexibility in distal elements18 and/or proximal elements 16 in the closed position to enable theseelements to move or flex with the opening or closing of the valveleaflets. This provides shock absorption and thereby reduces force onthe leaflets and minimizes the possibility for tearing or other traumato the leaflets. Such mobility or flexibility may be provided by using aflexible, resilient metal or polymer of appropriate thickness toconstruct the distal elements 18. Also, the locking mechanism of thefixation device (described below) may be constructed of flexiblematerials to allow some slight movement of the proximal and distalelements even when locked. Further, the distal elements 18 can beconnected to the coupling mechanism 19 or to actuation mechanism 58 by amechanism that biases the distal element into the closed position(inwardly) but permits the arms to open slightly in response to forcesexerted by the leaflets. For example, rather than being pinned at asingle point, these components may be pinned through a slot that alloweda small amount of translation of the pin in response to forces againstthe arms. A spring is used to bias the pinned component toward one endof the slot.

FIGS. 8A-8B, 9A-9B, 10A-10B, 11A-11B, and FIGS. 12-14 illustrateembodiments of the fixation device 14 of FIG. 7 in various possiblepositions during introduction and placement of the device 14 within thebody to perform a therapeutic procedure. FIG. 8A illustrates anembodiment of an interventional tool 10 delivered through a catheter 86.It may be appreciated that the interventional tool 10 may take the formof a catheter, and likewise, the catheter 86 may take the form of aguide catheter or sheath. However, in this example the termsinterventional tool 10 and catheter 86 will be used. The interventionaltool 10 comprises a fixation device 14 coupled to a shaft 12 and thefixation device 14 is shown in the closed position. FIG. 8B illustratesa similar embodiment of the fixation device of FIG. 8A in a larger view.In the closed position, the opposed pair of distal elements 18 arepositioned so that the engagement surfaces 50 face each other. Eachdistal element 18 comprises an elongate arm 53 having a cupped orconcave shape so that together the arms 53 surround the shaft 12 andoptionally contact each other on opposite sides of the shaft. Thisprovides a low profile for the fixation device 14 which is readilypassable through the catheter 86 and through any anatomical structures,such as the mitral valve. In addition, FIG. 8B further includes anactuation mechanism 58. In this embodiment, the actuation mechanism 58comprises two legs 68 which are each movably coupled to a base 69. Thebase 69 is joined with an actuator rod 64 which extends through theshaft 12 and is used to manipulate the fixation device 14. In someembodiments, the actuator rod 64 attaches directly to the actuationmechanism 58, particularly the base 69. However, the actuator rod 64 mayalternatively attach to a stud 74 which in turn is attached to the base69. In some embodiments, the stud 74 is threaded so that the actuatorrod 64 attaches to the stud 74 by a screw-type action. However, the rod64 and stud 74 may be joined by any mechanism which is releasable toallow the fixation device 14 to be detached from shaft 12. Other aspectsof the actuator rod and its coupling with the fixation device aredisclosed below.

FIGS. 9A-9B illustrate the fixation device 14 in the open position. Inthe open position, the distal elements 18 are rotated so that theengagement surfaces 50 face a first direction. Distal advancement of thestud 74 relative to coupling member 19 by action of the actuator rod 64applies force to the distal elements 18 which begin to rotate aroundjoints 76 due to freedom of movement in this direction. Such rotationand movement of the distal elements 18 radially outward causes rotationof the legs 68 about joints 80 so that the legs 68 are directed slightlyoutwards. The stud 74 may be advanced to any desired distancecorrelating to a desired separation of the distal elements 18. In theopen position, engagement surfaces 50 are disposed at an acute anglerelative to shaft 12, and are preferably at an angle of between 90 and180 degrees relative to each other. In one embodiment, in the openposition the free ends 54 of arms 53 have a span therebetween of about10-20 mm, usually about 12-18 mm, and preferably about 14-16 mm.

Proximal elements 16 are typically biased outwardly toward arms 53. Theproximal elements 16 may be moved inwardly toward the shaft 12 and heldagainst the shaft 12 with the aid of proximal element lines 90 which canbe in the form of sutures, wires, nitinol wire, rods, cables, polymericlines, or other suitable structures. The proximal element lines 90 maybe connected with the proximal elements 16 by threading the lines 90 ina variety of ways. When the proximal elements 16 have a loop shape, asshown in FIG. 9A, the line 90 may pass through the loop and double back.When the proximal elements 16 have an elongate solid shape, as shown inFIG. 9B, the line 90 may pass through one or more of the openings 63 inthe element 16. Further, a line loop 48 may be present on a proximalelement 16, also illustrated in FIG. 9B, through which a proximalelement line 90 may pass and double back. Such a line loop 48 may beuseful to reduce friction on proximal element line 90 or when theproximal elements 16 are solid or devoid of other loops or openingsthrough which the proximal element lines 90 may attach. A proximalelement line 90 may attach to the proximal elements 16 by detachablemeans which would allow a single line 90 to be attached to a proximalelement 16 without doubling back and would allow the single line 90 tobe detached directly from the proximal element 16 when desired. Examplesof such detachable means include hooks, snares, clips or breakablecouplings, to name a few. By applying sufficient tension to the proximalelement line 90, the detachable means may be detached from the proximalelement 16 such as by breakage of the coupling. Other mechanisms fordetachment may also be used. Similarly, a lock line 92 may be attachedand detached from a locking mechanism by similar detachable means.

In the open position, the fixation device 14 can engage the tissue whichis to be approximated or treated. The embodiment illustrated in FIGS.7-9B is adapted for repair of the mitral valve using an antegradeapproach from the left atrium. The interventional tool 10 is advancedthrough the mitral valve from the left atrium to the left ventricle. Thedistal elements 18 are oriented to be perpendicular to the line ofcoaptation and then positioned so that the engagement surfaces 50contact the ventricular surface of the valve leaflets, thereby graspingthe leaflets. The proximal elements 16 remain on the atrial side of thevalve leaflets so that the leaflets lie between the proximal and distalelements. In this embodiment, the proximal elements 16 have frictionalaccessories, such as barbs 60 which are directed toward the distalelements 18. However, neither the proximal elements 16 nor the barbs 60contact the leaflets at this time.

The interventional tool 10 may be repeatedly manipulated to repositionthe fixation device 14 so that the leaflets are properly contacted orgrasped at a desired location. Repositioning is achieved with thefixation device in the open position. In some instances, regurgitationmay also be checked while the device 14 is in the open position. Ifregurgitation is not satisfactorily reduced, the device may berepositioned and regurgitation checked again until the desired resultsare achieved.

It may also be desired to invert the fixation device 14 to aid inrepositioning or removal of the fixation device 14. FIGS. 10A-10Billustrate the fixation device 14 in the inverted position. By furtheradvancement of stud 74 relative to coupling member 19, the distalelements 18 are further rotated so that the engagement surfaces 50 faceoutwardly and free ends 54 point distally, with each arm 53 forming anobtuse angle relative to shaft 12. The angle between arms 53 ispreferably in the range of about 270 to 360 degrees. Further advancementof the stud 74 further rotates the distal elements 18 around joints 76.This rotation and movement of the distal elements 18 radially outwardcauses rotation of the legs 68 about joints 80 so that the legs 68 arereturned toward their initial position, generally parallel to eachother. The stud 74 may be advanced to any desired distance correlatingto a desired inversion of the distal elements 18. Preferably, in thefully inverted position, the span between free ends 54 is no more thanabout 20 mm, usually less than about 16 mm, and preferably about 12-14mm. In this illustration, the proximal elements 16 remain positionedagainst the shaft 12 by exerting tension on the proximal element lines90. Thus, a relatively large space may be created between the elements16, 18 for repositioning. In addition, the inverted position allowswithdrawal of the fixation device 14 through the valve while minimizingtrauma to the leaflets. Engagement surfaces 50 provide an atraumaticsurface for deflecting tissue as the fixation device is retractedproximally. It should be further noted that barbs 60 are angled slightlyin the distal direction (away from the free ends of the proximalelements 16), reducing the risk that the barbs will catch on or laceratetissue as the fixation device is withdrawn.

Once the fixation device 14 has been positioned in a desired locationagainst the valve leaflets, the leaflets may then be captured betweenthe proximal elements 16 and the distal elements 18. FIGS. 11A-11Billustrate the fixation device 14 in such a position. Here, the proximalelements 16 are lowered toward the engagement surfaces 50 so that theleaflets are held therebetween. In FIG. 11B, the proximal elements 16are shown to include barbs 60 which may be used to provide atraumaticgripping of the leaflets. Alternatively, larger, more sharply pointedbarbs or other penetration structures may be used to pierce the leafletsto more actively assist in holding them in place. This position issimilar to the open position of FIGS. 9A-9B, however the proximalelements 16 are now lowered toward arms 53 by releasing tension onproximal element lines 90 to compress the leaflet tissue therebetween.At any time, the proximal elements 16 may be raised and the distalelements 18 adjusted or inverted to reposition the fixation device 14,if regurgitation is not sufficiently reduced.

After the leaflets have been captured between the proximal and distalelements 16, 18 in a desired arrangement, the distal elements 18 may belocked to hold the leaflets in this position or the fixation device 14may be returned to or toward a closed position. Such locking will bedescribed in a later section. FIG. 12 illustrates the fixation device 14in the closed position wherein the leaflets (not shown) are captured andcoapted. This is achieved by retraction of the stud 74 proximallyrelative to coupling member 19 so that the legs 68 of the actuationmechanism 58 apply an upwards force to the distal elements 18 which inturn rotate the distal elements 18 so that the engagement surfaces 50again face one another. The released proximal elements 16 which arebiased outwardly toward distal elements 18 are concurrently urgedinwardly by the distal elements 18. The fixation device 14 may then belocked to hold the leaflets in this closed position as described below.

As shown in FIG. 13, the fixation device 14 may then be released fromthe shaft 12. As mentioned, the fixation device 14 is releasablycoupleable to the shaft 12 by coupling member 19 (best seen in FIG. 17).FIG. 13 illustrates the coupling structure, a portion of the shaft 12 towhich the coupling member 19 of the fixation device 14 attaches. Asshown, the proximal element lines 90 may remain attached to the proximalelements 16 following detachment from shaft 12 to function as a tetherto keep the fixation device 14 connected with the catheter 86.Optionally, a separate tether coupled between shaft 12 and fixationdevice 14 may be used expressly for this purpose while the proximalelement lines 90 are removed. In any case, the repair of the leaflets ortissue may be observed by non-invasive visualization techniques, such asechocardiography, to ensure the desired outcome. If the repair is notdesired, the fixation device 14 may be retrieved with the use of thetether or proximal element lines 90 so as to reconnect coupling member19 with shaft 12.

In an exemplary embodiments, proximal element lines 90 are elongatedflexible threads, wire, cable, sutures or lines extending through shaft12, looped through proximal elements 16, and extending back throughshaft 12 to its proximal end. When detachment is desired, one end ofeach line may be released at the proximal end of the shaft 12 and theother end pulled to draw the free end of the line distally through shaft12 and through proximal element 16 thereby releasing the fixationdevice.

FIG. 14 illustrates a released fixation device 14 in a closed position.As shown, the coupling member 19 remains separated from the shaft 12 ofthe interventional tool 10 and the proximal elements 16 are deployed sothat tissue (not shown) may reside between the proximal elements 16 anddistal elements 18.

While the above described embodiments of the invention utilize apush-to-open, pull-to-close mechanism for opening and closing distalelements 18, it should be understood that a pull-to-open, push-to-closemechanism is equally possible. For example, distal elements 18 may becoupled at their proximal ends to stud 74 rather than to coupling member19, and legs 68 may be coupled at their proximal ends to coupling member19 rather than to stud 74. In this example, when stud 74 is pusheddistally relative to coupling member 19, distal elements 18 would close,while pulling on stud 74 proximally toward coupling member 19 would opendistal elements 18.

In some situations, the valve leaflets may fully or partially detachfrom the fixation device due to poor leaflet insertion between theproximal and distal elements. Evaluation of valve leaflet insertion inthe fixation device is therefore performed using standard imagingtechnology such as echocardiography and fluoroscopy. However, dependingon the angle and/or position of the proximal and distal elementsrelative to the delivery catheter, it can be challenging to assess thedepth of valve leaflet insertion into the fixation device, or todifferentiate between the leaflets and the proximal and distal elementsof the fixation device. Visualization is therefore preferably performedwith the distal elements in a more open configuration with the distalelements displaced from one another. However, since many currentembodiments of the fixation device only permit the proximal elements toopen up to an included angle of about 85°, the distal elements thereforemust be closed up to an included angle of between about 45° andpreferably 60° in order securely grasp the valve leaflets between theproximal and distal elements. While this configuration helps an operatorvisualize and differentiate between the valve leaflets and the fixationdevice, it is preferable to further open up the distal elements to anincluded angle of greater than 90°, and more preferably to 120° or more.Thus, it would be desirable to modify the proximal elements to open upfurther.

FIGS. 15A-15H illustrate an embodiment of a fixation device similar tothe device of FIGS. 7A-14, with a major difference being that thisembodiment includes a gripper pusher. FIG. 15A illustrates fixationdevice 14 that generally takes the same form as fixation device 14previously described. In addition to the features previously described,fixation device 14 also includes a gripper pusher 81. The gripper pusher81 deflects radially outward resulting in a bowed region 83 that expandsoutward until the bowed region 83 engages a superior surface of theproximal elements 16. As the bowed region 83 continues to deflectradially outward, it further pushes on the proximal elements 16 suchthat the proximal elements are deflected and rotated outward toward theengagement surface of the distal elements 18. Thus, the proximalelements 16 may be deflected outward further than they normally would,and therefore the valve leaflets may be captured between the proximaland distal elements when the distal elements are disposed in a more openposition with a larger included angle therebetween. In preferredembodiments, the included angle between the distal elements is greaterthan about 90°, preferably greater than about 110°, and more preferablygreater than about 120°. In the embodiment of FIG. 15A, the gripperpusher 81 includes two arms formed from a metal, polymer or otherwire-like material. Exemplary materials include cobalt chromium alloy,stainless steel, nitinol, and the like. Polymers may also be used tofabricate the gripper pusher. The gripper pusher 81 may be actuated tobow outwards upon application of an axially oriented compressive forcethat is generally parallel to the longitudinal axis of the gripperpusher arms. During compression, the gripper pusher bows outward formingbowed region 83. In other embodiments, the gripper pusher may be aspring which is resiliently biased to bow outward forming bowed region83. However, when proximal element lines (not illustrated here) aretensioned to lift the proximal elements 16, the gripper pusher springswill collapse to a reduced profile.

FIG. 15B illustrates the fixation device 14 having a covering for tissueingrowth that is substantially the same as discussed in FIGS. 16A-16Cbelow, and with the gripper pusher 81 expanded such that the proximalelements 16 (also referred to as gripping elements) are in engagementwith the distal elements 18 (also referred to as fixation elements). Thevalve leaflets (not shown for convenience) are pinched therebetween.FIG. 15C illustrates the gripper pusher 81 in the collapsedconfiguration. The bowed region 83 collapses, allowing the proximalelements 16 to retract towards shaft 12, allowing the valve leaflets(not shown) to be released from the fixation device 14. The gripperpusher 83 is offset from the proximal elements 16 so that the proximalelements can retract without interfering with the gripper pusher 81.

FIG. 15D highlights the gripper pusher 83 which preferably includes twospring arms 99. Each arm 99 is formed from wire or machined from a sheetor other stock material and in this embodiment has a rectangularcross-section, although other cross-sections are also contemplated. Adistal portion 91 of each arm 99 has a notched region 93 forming a pairof fingers that can engage with a boss or other attachment mechanism onthe fixation device. The notch may be released from the boss when thefixation device 14 is detached from the delivery catheter shaft 12.Additionally, each arm includes two bowed regions, or peaks, including alarger distal bowed region 83, and a smaller proximal bowed region 95.The larger bowed region 83 flares outwardly a greater distance so as toengage and push the proximal elements 16 into engagement with the distalelements 18. When the distal bowed region 83 relaxes and collapses awayfrom the proximal elements 16, or when collapsed by retraction of theproximal elements, the smaller proximal bowed regions 95 expand radiallyoutward. An attachment ring or coupling collar 97 is adjacent nose 318(described in greater detail below) and is slidably disposed over theshaft 12 and allows coupling of the gripper arms 99 to the shaft 12.FIG. 15E illustrates the distal bowed region 83 in engagement with theproximal elements 16, and also illustrates engagement of the notch 93 onthe distal portion of each arm 99 with a boss 94 on the fixation device14.

Additional components may be provided to facilitate maintaining thealignment of the gripper pushers 83 relative to the delivery cathetershaft 12. FIG. 15E1 shows a cross-sectional view of the deliverycatheter shaft 12 with the gripper pusher 83 and FIG. 15E2 shows a sideview of the same. As shown in FIGS. 15E1 and 15E2, each arm 99 may havea slot 8112 and the delivery catheter shaft 12 may have one or moreprotrusions 1281 which the slots 8112 straddle to maintain the alignmentof the gripper pusher 83 relative to the delivery catheter shaft 12. Theregion of the arm 99 having the slot 8112 is wider than the remainder ofthe arm 99 to accommodate the slot 8112. The greater width may alsoallow the arm 99 to be pushed to the side without becoming misalignedrelative to the delivery catheter shaft 12. FIG. 15E3 shows across-sectional view of the delivery catheter shaft 12 and FIG. 15E4shows a side view of the same. As shown in FIGS. 15E3 and 15E4, each arm99 may have one or more inwardly bowed regions 8212 and the deliverycatheter shaft 12 may have one or more troughs 1282 which accommodatethe inwardly bowed regions 8212 to maintain the alignment of the gripperpusher 83 relative to the delivery catheter shaft 12.

FIG. 15F illustrates a top view of the gripper pusher 81 having two arms99. FIG. 15F illustrates that the two arms 99 are offset from oneanother such that in this exemplary embodiment, angle α is about 160°and angle θ is about 200°, as opposed to positioning the arms 180° apartfrom one another. Asymmetrically positioning the arms about the shaftcreates a larger gap on one side, and allows the proximal elements 16 toavoid colliding with the gripper pusher arms 99 when the proximalelements retract against shaft 12. FIG. 15G is a top view of collar 97,and FIG. 15H is a side view of gripper pusher arm 99. A cutout 98 on oneside of arm 99 creates additional room between arms 99, thereby alsohelping to prevent the proximal elements 16 from interfering with thegripper pusher 83 when the proximal elements 16 are retracted. Thecutouts are on both arms 99 and face the larger gap represented by angleθ to maximize room for the proximal elements 16.

As described above, for example, with reference to FIGS. 9A and 9B,actuation of the proximal elements 16 may be accomplished by using oneor more proximal element lines or actuators 90. Such actuation can beachieved in various ways. For example, as shown in FIG. 15I, theproximal element actuators 90A and 90B could be threaded through lineloops 48A and 48B, which are disposed on the radially outward andproximal sides of the proximal elements 16A and 16B, respectively. Thedistal ends of proximal element actuators 90A and 90B may compriseclosed loops 95A and 95B, which encircle the shaft 12 and the couplingmember 19 shown in FIG. 15I as coupled together. As discussed above, theshaft 12 and the coupling member 19 can be releasably coupled together.To have the closed loops 95A and 95B surround shaft 12 and the couplingmember 19, the closed loops 95A and 95B are placed over the shaft 12and/or the coupling member 19 prior to the coupling shaft 12 and thecoupling member 19 together. When the closed loops 95A and 95B encirclethe shaft 12 and the coupling member 19, the closed loops 95A and 95Bhold the distal ends of the proximal element actuators 90A and 90B inplace relative to the shaft 12 and the coupling member 19 and restrictthe degree to which the proximal element actuators 90A and 90B can beretracted. By being threaded through the line loops 48A and 48B, theproximal element actuators 90A and 90B are mechanically linked to theproximal elements 16A and 16B, respectively. Thus, as shown in FIG. 15J,when the proximal element actuators 90A and 90B are retracted proximallyin a direction 96, they move the proximal elements 16A and 16B away fromthe distal elements 18A and 18B, respectively. Similarly, pushing theproximal element actuators 90A and 90B distally moves the proximalelements 16A and 16B toward the distal elements 18A and 18B.

The proximal element actuators 90A and 90B may be moved so that theproximal elements 16A and 16B are moved at a variety of angles anddistances from the distal elements 18A and 18B. And, the degree to whichthe proximal element actuators 90A and 90B are pushed or pulled can bemaintained to keep the positions the proximal elements 16A and 16B haverelative to the distal elements 18. For example, as shown in FIG. 15K,the proximal element actuators 90A and 90B are pulled proximally andmaintained in the position shown so as to maintain the proximal elements16A and 16B in an intermediate position relative to the distal elements18. This intermediate position is between the position the proximalelements 16A and 16B are biased toward and that in which the proximalelements 16A and 16B are fully retracted as in FIG. 15J. As shown inFIG. 15N, once the proximal elements 16A and 16B are in a desiredposition, the shaft 12 and the coupling member 19 can be decoupled sothat proximal retraction of the proximal element actuators 90A and/or90B decouples the proximal element lines from the proximal elements 16.Thus, the fixation device 14 can be left in place while the shaft 12,the proximal element actuators 90A and 90B, and other parts can beremoved from a site of operation. As shown in FIGS. 15I through 15O, thefixation device 14 typically includes a covering 100 substantially thesame as discussed in FIGS. 16A-16C below.

It may be desirable to provide for independent actuation of the proximalelements 16A and 16B. For example, as shown in FIG. 15L, the proximalelement actuator 90A is proximally retracted and rotates the proximalelement 16A away from the distal element 18A, while the proximal elementactuator 90B is pushed distally and rotates the proximal element 16Btoward the distal element 18B. Similarly, as shown in FIG. 15M, theproximal element actuator 90A is left alone, allowing the proximalelement 16A to maintain the position it is biased toward, while theproximal element actuator 90B is proximally retracted, moving theproximal element 16B away from the distal element 18B. Providing for theindependent actuation of the proximal elements 16A and 16B allowsleaflets to be independently grasped by the proximal elements 16A and16B and the distal elements 18A and 18B. Thus, the fixation device 14can coapt leaflets more easily and at more optimal locations. Forexample, as opposed to grasping two leaflets simultaneously, a firstleaflet can be grasped at a desired position and the fixation device 14can then be repositioned so that a second leaflet can be grasped at amore optimal position. Alternatively, leaflets may be still besimultaneously grasped if desired as the independently actuatableproximal element actuators can still be moved simultaneously. Also,after leaflets are grasped, they can be released and the leaflets can begrasped again, for example, if the leaflets are malcoapted at the firstgrasp.

Embodiments of the fixation device similar to the devices describedabove may include both a gripper pusher 81 and independently actuatableproximal elements 16A and 16B, as shown for example in FIG. 15O. Havingboth a gripper pusher 81 and independently actuatable proximal elements16A and 16B may allow the fixation device to have many of the advantagesdescribed above such as to more accurately and more strongly graspleaflets.

FIG. 15P shows the distal end of a proximal element actuator 90. Theproximal element actuator 90 comprises a round section 90R and a flatsection 90F distal of the round section 90R. When this proximal elementactuator 90 is threaded through a proximal element 16 and coupled to afixation device 14, the flatter portion of the flat section may bepositioned so that it faces proximal element 16. As the proximal elementactuator 90 is proximally advanced, it will therefore tend to deflect itin the direction toward the proximal element 16 instead of in otherdirections and push the proximal element. The proximal element actuator90 further comprises a looped end 95. As shown in FIG. 15P, the loopedend 95 may comprise a separate loop of wire attached with the distal endof the flat section 90F at its distal end, for example, with solder 94.

The proximal element actuator 90 may also be releaseably coupled to thefixation device 14 in other ways. For example, as shown in FIGS. 15Q and15R, the proximal element actuator 90 comprises a spiraled distalsection 95L which is releaseably coupled to the fixation device 14. Thespiraled distal section 95L is wrapped about the shaft 12 and/or thecoupling mechanism 19. Retracting the proximal element actuator 90 withsufficient force may deform the spiraled distal section 95L so that itis released from the fixation device 14. Alternatively or incombination, the spiraled distal section 95L may comprise a shape memorymaterial such that the spiraled distal section 95L is straightened uponthe application of a sufficient amount of heat, facilitating theproximal retraction of the proximal element actuator 90 away from thefixation device 14.

The proximal element actuator 90 may be releaseably coupled to thefixation device 14 by suture. As shown in FIGS. 15S and 15T, a proximalelement actuator 90 is releaseably coupled to the fixation device 14 viaa suture knot 95S. Each proximal actuator 90 may be coupled to thefixation device 14 by a separate suture knot 95S. Alternatively, a pairof proximal actuators 90 may be coupled to the fixation device 14 by asingle suture knot.

A proximal element actuator 90 may comprise an enlarged section 90T asshown in FIGS. 15U and 15V. The diameter of the enlarged section 90Texceeds the diameter of the opening of the loop line 48. As the proximalelement actuator 90 is retracted, the loop line 48 restricts theproximal movement of the enlarged section 90T. Thus, a pulling force isexerted on the loop line 48 and proximal element 16, which facilitatesthe actuation of a proximal element 16. The enlarged section 90T may bea sleeve attached over the proximal element actuator 90.

The proximal element actuator 90 may be releaseably coupled to theproximal element 16 at the radially outward ends of the proximal element16 by an attachment device, for example, as shown in FIGS. 15W1 to 15W2.The attachment device may comprise a ring 90CR as shown in a perspectiveview in FIG. 15W1, a short clip 90CC as shown in a perspective view inFIG. 15W2, or a long clip 90CL as shown in FIGS. 15W3 to FIG. 15W5. FIG.15W3 shows a perspective view of the long clip 90CL attaching theproximal element actuator 90 to a proximal element 16. FIGS. 15W4 and15W5 show a front and side view of the same, respectively. The long clip90CL may comprise a pair of legs 90CLL which traverse the length of theproximal element 16. As shown in FIG. 15W5, a leg 90CLL is disposedbetween two rows of barbs 60.

The above described attachment devices may be spring loaded to latchonto or sized to slip fit into the radially outward ends of the proximalelement 16. As the proximal element actuator 90 is retracted, theattachment device continues to be attached to the proximal element 16.As the proximal element 16 is rotated to be substantially parallel to ashaft 19, however, further proximal retraction of the proximal elementactuator 90 can release the attachment device from the outer end of theproximal element 16. A mechanical mechanism may be provided to limit thedegree to which the proximal element actuator 90 can be proximallyretracted so that the attachment device is not detached inadvertently.Instead, detachment will occur only upon retraction of the wholedelivery device, including the proximal element actuators 90, from thefixation device 14.

The proximal element actuator 90 may comprise two lines: an actuationline 90AA and a release line 90RR, for example, as shown in FIGS. 15X1to 15X3. FIG. 15X1 shows a perspective view of an radially outer end ofa proximal element 16 having an aperture 48A. FIG. 15X2 shows across-sectional view of the same. The actuation line 90AA has a loopedend 90AAL which is threaded through the aperture 48A to cross throughproximal element 16. The release line 90RR is threaded through theportion of the looped end 90AAL. In FIG. 15X3, the actuation line 90AAand the release line 90RR are similarly positioned through loop line 48of proximal element 16. While the actuation line 90AA and the releaseline 90RR are positioned in the arrangement shown in FIGS. 15X1 to 15X3,retracting the actuation line 90AA rotates the proximal element 16relative to a distal element 18 similarly to the embodiments describedabove. Retracting the release line 90RR so that it no longer is threadedthrough the looped end 90AAL allows the actuation line to be retractedaway from the proximal element 16.

In many embodiments, the shaft 12 and the coupling member 19 arereleaseably coupled together via an L-locking mechanism. For example, asshown in FIG. 15Y1, the proximal element actuator 90 may comprise around T-shaped end 90T distal of the flat section 90F and the shaft 12may comprise L-shaped ends 12L. As shown in the perspective view of FIG.15Y2, the proximal element actuator 90 is releaseably coupled to thecoupling member 19 when it and shaft 12 are placed into the channel 19Cof the coupling member 19. As the shaft 12 is placed through the channel19C, the L-shaped ends 12L are forced inwardly until they reachapertures 19A. At that point, the L-shaped ends 12L expand outwardly tofit into the apertures 19A, thereby locking the shaft 12 in placerelative to the coupling member 19, as shown in cross-sectional view ofFIG. 15Y3. The round T-shaped distal end 90T will typically be placed inthe channel 19C prior to the shaft 12. As shown in FIG. 15Y3, the roundT-shaped distal end 90T then becomes trapped in the space 19CA betweenthe channel 19C and a wider portion of the shaft 12 when the shaft isplaced therein. Other L-locking or other locking mechanisms aredescribed in commonly assigned U.S. patent application Ser. No.12/393,452 entitled “Detachment Mechanism for Implantable FixationDevices” and filed Feb. 26, 2009, the full contents of which areincorporated herein by reference.

The round T-shaped end 90T of the proximal element actuator 90 may alsobe used to facilitate releaseably coupling the proximal element line 90to the shaft 12 and coupling member 19 is many other ways. For example,as shown in FIG. 15Z1, the L-shaped end 12L of the shaft 12 may compriseat least one proximal element line slot 12S. As shown in FIGS. 15Z3 and15Z4, the T-shape end 90T of the proximal element actuator 90 is slidinto the proximal element line slot 12L. Then, the shaft 12 is placedinto the coupling member 19, thereby also locking the proximal elementline 90 in place. As shown in FIG. 15Z5, removing the shaft 12 from thecoupling member 19 allows the proximal element line 90 to be slid out ofthe proximal element line slot 12S of L-shaped end 12L, therebydecoupling the proximal element actuator 90 from both the shaft 12 andthe coupling device 19.

As shown in FIG. 15AA1, the proximal element actuator 90 may comprise aflat T-shaped end 90TF. The shaft 12 may further comprise an innerdistal covering 1511 surrounding a distal portion of the shaft 12 and anouter distal covering 1521 surrounding the inner distal covering. Theinner distal covering 1511 will typically be in a fixed positionrelative to the shaft 12 while the outer distal covering will bemoveable relative to the shaft 12 at a range determined by tabs 1515 ofinner distal covering 1511 placed through side channels 1525 of theouter distal covering 1521. To releaseably couple the proximal elementactuator 90 to the shaft 12 and coupling line 19, the T-shaped end 90TFis fit into a T-shaped cutout 1513 of inner distal covering 1511, andwhen the shaft 12 is placed into the coupling device 19, the couplingdevice 19 pushes the outer distal covering 1521 over the inner distalcovering 1511 to cover the T-shaped cutout 1513 as well as the T-shapedend 90TF, as shown in FIG. 15AA2. In some embodiments, the outer distalcovering 1521 may be spring loaded against the inner distal cover 1523so that tend to maintain their relative positions shown in FIG. 15AA1.

Proximal element actuators 90 may be releaseably coupled to the fixationdevice 14 in a variety of ways using variations of inner and outerdistal collars over the distal portion of shaft 12, for example, asshown in FIGS. 15AB1 to 15AB7. FIG. 15AB1 shows an inner distal collar1511A having a pair of T-shaped cutouts 1513 and a tab 1514. FIG. 15AB3shows an outer distal collar 1521A having a channel 1524. The channel1524 guides the inner distal collar 1511A via its tab 1514 as the innerdistal collar 1511A is slid into the outer distal collar 1521A, forexample as shown in FIGS. 15AB3 through 15AB5. As in the embodimentshown in FIGS. 15AA1 and 15AA2, to releaseably couple the proximalelement actuators 90 to the shaft 12 and coupling member 19, theT-shaped end 90TF is fit into a T-shaped cutout 1513 of inner distalcollar 1511S. When the shaft 12 is placed into the coupling device 19,the coupling member 19 pushes the outer distal collar 1521S over theinner distal collar 1511S to cover the T-shaped cutout 1513 as well asthe T-shaped end 90TF, as shown in FIGS. 15AB6 and 15AB7.

As described below, a delivery device or delivery catheter 300 may beused to introduce and position fixation devices as described above. Inembodiments of the invention with independently actuatable proximalelement lines, the handle 304 of the delivery catheter will typicallyinclude control mechanisms for the independently actuable proximalelement lines. For example, a control mechanism may comprise a pair ofindependently actuable proximal element line handles 393A and 393Bplaced in parallel, as shown in FIG. 15AC1, or placed coaxially, asshown in FIG. 15AC2. The proximal element line handles 393A and 393B arecoupled to proximal element lines 90A and 90B and may share a common orinterconnecting lumens in the delivery device. Stop may be provided tolimit the degree to which the proximal element line handles 393A and393B can be retracted or advanced, thereby limiting the degree to whichthe proximal element actuators 90A and 90B can be retracted or advanced.In some embodiments, for example, as shown by FIGS. 15AC3 and 15AC4, aproximal element line handle 393 may be actuated by a rotatable switch395 attached to it.

B. Covering on Fixation Device

The fixation device 14 may optionally include a covering. The coveringmay assist in grasping the tissue and may later provide a surface fortissue ingrowth. Ingrowth of the surrounding tissues, such as the valveleaflets, provides stability to the device 14 as it is further anchoredin place and may cover the device with native tissue thus reducing thepossibility of immunologic reactions. The covering may be comprised ofany biocompatible material, such as polyethylene terepthalate,polyester, cotton, polyurethane, expanded polytetrafluoroethylene(ePTFE), silicon, or various polymers or fibers and have any suitableform, such as a fabric, mesh, textured weave, felt, looped or porousstructure. Generally, the covering has a low profile so as not tointerfere with delivery through an introducer sheath or with graspingand coapting of leaflets or tissue.

FIGS. 16A-16C illustrate a covering 100 on the fixation device 14wherein the device 14 is in various positions. FIG. 16A shows thecovering 100 encapsulating the distal elements 18 and the actuationmechanism 58 while the device 14 is in the open position. Thus, theengagement surfaces 50 are covered by the covering 100 which helps tominimize trauma on tissues and provides additional friction to assist ingrasping and retaining tissues. FIG. 16B shows the device 14 of FIG. 16Ain the inverted position. The covering 100 is loosely fitted and/or isflexible or elastic such that the device 14 can freely move to variouspositions and the covering 100 conforms to the contours of the device 14and remains securely attached in all positions. FIG. 16C shows thedevice 14 in the closed position. Thus, when the fixation device 14 isleft behind as an implant in the closed position, the exposed surfacesof the device 14 are substantially covered by the covering 100. It maybe appreciated that the covering 100 may cover specific parts of thefixation device 14 while leaving other parts exposed. For example, thecovering 100 may comprise sleeves that fit over the distal elements 18and not the actuation mechanism 58, caps that fit over the distal ends54 of the distal elements 18 or pads that cover the engagement surfaces50, to name a few. It may be appreciated that, the covering 100 mayallow any frictional accessories, such as barbs, to be exposed. Also,the covering 100 may cover the proximal elements 16 and/or any othersurfaces of the fixation device 14. In any case, the covering 100 shouldbe durable to withstand multiple introduction cycles and, when implantedwithin a heart, a lifetime of cardiac cycles.

The covering 100 may alternatively be comprised of a polymer or othersuitable materials dipped, sprayed, coated or otherwise adhered to thesurfaces of the fixation device 14. Optionally, the polymer coating mayinclude pores or contours to assist in grasping the tissue and/or topromote tissue ingrowth.

Any of the coverings 100 may optionally include drugs, antibiotics,anti-thrombosis agents, or anti-platelet agents such as heparin,COUMADIN® (Warfarin Sodium), to name a few. These agents may, forexample, be impregnated in or coated on the coverings 100. These agentsmay then be delivered to the grasped tissues surrounding tissues and/orbloodstream for therapeutic effects.

C. Fixation Device Locking Mechanisms

As mentioned previously, the fixation device 14 optionally includes alocking mechanism for locking the device 14 in a particular position,such as an open, closed or inverted position or any positiontherebetween. It may be appreciated that the locking mechanism includesan unlocking mechanism which allows the device to be both locked andunlocked. FIGS. 17-20 illustrate an embodiment of a locking mechanism106. Referring to FIG. 17, in this embodiment, the locking mechanism 106is disposed between the coupling member 19 and the base 69 of theactuation mechanism 58. The base 69 is fixedly attached to the stud 74which extends through the locking mechanism 106. The stud 74 isreleasably attached to the actuator rod 64 which passes through thecoupling member 19 and the shaft 12 of the interventional tool 10. Thebase 69 is also connected to the legs 68 of the actuation mechanism 58which are in turn connected to the distal elements 18.

FIG. 17 also illustrates the proximal elements 16, which in thisembodiment straddle the locking mechanism and join beneath the lockingmechanism 106. The proximal elements 16 are shown supported by proximalelement lines 90. The proximal elements 16 are raised and lowered bymanipulation of the proximal element lines 90. In addition, lock lines92 are shown connected with a release harness 108 of the lockingmechanism 106. The lock lines 92 are used to lock and unlock the lockingmechanism 106 as will be described below. The proximal element lines 90and lock lines 92 may be comprised of any suitable material, typicallywire, nitinol wire, cable, suture or thread, to name a few. In addition,the proximal element lines 90 and/or lock lines 92 may include acoating, such as parylene. Parylene is a vapor deposited pinhole freeprotective film which is conformal and biocompatible. It is inert andprotects against moisture, chemicals, and electrical charge.

FIG. 18 provides a front view of the locking mechanism 106 of FIG. 17.However, here the proximal elements 16 are supported by a singleproximal element line 90 which is through both of the proximal elements16. In this arrangement both of the elements are raised and loweredsimultaneously by action of a single proximal element line 90. Whetherthe proximal elements 16 are manipulated individually by separateproximal element lines 90 or jointly by a single proximal element line90, the proximal element lines 90 may extend directly through openingsin the proximal elements and/or through a layer or portion of a covering100 on the proximal elements, or through a suture loop above or below acovering 100.

FIGS. 19-20 illustrate the locking mechanism 106 showing the lockingmechanism 106 in the unlocked and locked positions respectively.Referring to FIG. 19, the locking mechanism 106 includes one or morewedging elements, such as rolling elements. In this embodiment, therolling elements comprise a pair of barbells 110 disposed on oppositesides of the stud 74, each barbell having a pair of generallycylindrical caps and a shaft therebetween. The barbells 110 and the stud74 are preferably comprised of cobalt chromium or stainless steel,however any suitable material may be used. The barbells 110 aremanipulated by hooked ends 112 of the release harness 108. When anupwards force is applied to the harness 108 by the lock line 92(illustrated in FIG. 17), the hooked ends 112 raise the barbells 110against a spring 114, as shown in FIG. 19. This draws the barbells 110up along a sidewall or sloping surface 116 which unwedges the barbells110 from against the stud 74. In this position, the stud 74 is free tomove. Thus, when the lock line 92 raises or lifts the harness 108, thelocking mechanism 106 is in an unlocked position wherein the stud 74 isfree to move the actuation mechanism 58 and therefore the distalelements 18 to any desired position. Release of the harness 108 by thelock line 92 transitions the locking mechanism 106 to a locked position,illustrated in FIG. 20. By releasing the upwards force on the barbells110 by the hooked ends 112, the spring 114 forces the barbells 110downwards and wedges the barbells 110 between the sloping surface 116and the stud 74. This restricts motion of the stud 74, which in turnlocks the actuation mechanism 58 and therefore distal elements 18 inplace. In addition, the stud 74 may include one or more grooves 82 orindentations which receive the barbells 110. This may provide more rapidand positive locking by causing the barbells 110 to settle in a definiteposition, increase the stability of the locking feature by furtherpreventing movement of the barbells 110, as well as tangible indicationto the user that the barbell has reached a locking position. Inaddition, the grooves 82 may be used to indicate the relative positionof the distal elements 18, particularly the distance between the distalelements 18. For example, each groove 82 may be positioned to correspondwith a 0.5 or 1.0 mm decrease in distance between the distal elements18. As the stud 74 is moved, the barbells 110 will contact the grooves82; by counting the number of grooves 82 that are felt as the stud 74 ismoved, the user can determine the distance between the distal elements18 and can provide the desired degree of coaptation based upon leafletthickness, geometry, spacing, blood flow dynamics and other factors.Thus, the grooves 82 may provide tactile feedback to the user.

The locking mechanism 106 allows the fixation device 14 to remain in anunlocked position when attached to the interventional tool 10 duringgrasping and repositioning and then maintain a locked position when leftbehind as an implant. It may be appreciated, however, that the lockingmechanism 106 may be repeatedly locked and unlocked throughout theplacement of the fixation device 14 if desired. Once the final placementis determined, the lock line 92 and proximal element lines 90 areremoved and the fixation device is left behind.

FIGS. 21, 22A-22B illustrate another embodiment of a locking mechanism106. Referring to FIG. 21, in this embodiment, the locking mechanism 106is again disposed between the coupling member 19 and the base 69 of theactuation mechanism 58. The base 69 is connected to the stud 74 whichextends through the locking mechanism 106, and connects to an actuatorrod which extends through the coupling member 19 and the shaft 12 of theinterventional tool 10. The base 69 is also connected to the legs 68 ofthe actuation mechanism 58 which are in turn connected to the distalelements 18. FIG. 21 also illustrates the proximal elements 16 whichmanipulate the locking mechanism 106 in this embodiment. The lockingmechanism 106 comprises folded leaf structures 124 having overlappingportions 124 a, 124 b, each folded structure 124 being attached to aproximal element 16. In FIG. 21 and FIG. 22A, the folded structures 124are shown without the remainder of the locking mechanism 106 forclarity. Proximal elements 16 are flexible and resilient and are biasedoutwardly. The folded leaf structures 124 include holes 125 (FIG. 22B)in each overlapping portion 124 a, 124 b so that the stud 74 passesthrough the holes 125 of the portions 124 a, 124 b as shown. The lockingmechanism includes slots into which ends 123 of the folded leafstructures 124 are fixed. When the proximal elements 16 are in anundeployed position, as in FIG. 21, the folded leaf structures 124 liesubstantially perpendicular to the stud 74 so that the holes 125 in eachoverlapping portion are vertically aligned. This allows the stud 74 topass freely through the holes and the locking mechanism 106 isconsidered to be in an unlocked position.

Deployment of the proximal elements 16, as shown in FIG. 22A, tilts thefolded leaf structures 124 so as to be disposed in a non-perpendicularorientation relative to the stud 74 and the holes 125 are no longervertically aligned with one another. In this arrangement, the stud 74 isnot free to move due to friction against the holes of the folded leafstructure 124. FIG. 22B provides a larger perspective view of the foldedstructures 124 in this position. Thus, the locking mechanism 106 isconsidered to be in a locked position. This arrangement allows thefixation device 14 to maintain an unlocked position during grasping andrepositioning and then maintain a locked position when the proximalelements 16 are deployed and the fixation device 14 is left behind as animplant. It may be appreciated, however, that the locking mechanism 106may be repeatedly locked and unlocked throughout the placement of thefixation device 14 if desired.

FIGS. 23, 24A-24B illustrate another embodiment of a locking mechanism106. Referring to FIG. 22, in this embodiment, the locking mechanism 106is again disposed between the coupling member 19 and the base 69 of theactuation mechanism 58. And, the base 69 is connected to the stud 74which extends through the locking mechanism 106 and connects to anactuator rod which extends through the coupling member 19 and the shaftof the interventional tool 10. FIG. 22 illustrates the proximal elements16 which manipulate the locking mechanism 106 in this embodiment. Thelocking mechanism 106 comprises C-shaped structures 128, each C-shapedstructure 128 attached to a proximal element 16. The C-shaped structures128 hook around the stud 74 so that the stud 74 passes through the “C”of each structure 128 as shown in FIGS. 24A-24B. As shown, thestructures 128 cross each other and the “C” of each structure 128 faceseach other. A spring 130 biases the C-shaped structures into engagementwith one another. When the proximal elements are in an undeployedposition, as in FIG. 24A, the C-shaped structures 128 are urged into anorientation more orthogonal to the axial direction defined by stud 74,thus bringing the “C” of each structure 128 into closer axial alignment.This allows the stud 74 to pass freely through the “C” of each structure128. Deployment of the proximal elements 16 outwardly urges the C-shapedstructures into a more angular, non-orthogonal orientation relative tostud 74 causing the sidewalls of the “C” of each structure 128 to engagestud 74 more forcefully. In this arrangement, the stud 74 is not free tomove due to friction against the “C” shaped structures 128.

D. Additional Embodiments of Fixation Devices

In other embodiments, the proximal elements may be manipulated toenhance gripping. For example, the proximal elements may be lowered tograsp leaflets or tissue between the proximal and distal elements, andthen the proximal elements may be moved to drag the leaflets or tissueinto the fixation device. In another example, the proximal elements maybe independently lowered to grasp the leaflets or tissue. This may beuseful for sequential grasping. In sequential grasping, one proximalelement is lowered to capture a leaflet or tissue portion between theproximal and distal elements. The fixation device is then moved,adjusted or maneuvered to a position for grasping another leaflet ortissue portion between another set of proximal and distal elements. Inthis position, the second proximal element is then lowered to grasp thisother leaflet or tissue portion.

Other exemplary embodiments of fixation devices are disclosed in U.S.Pat. Nos. 7,563,267 (Attorney Docket No. 020489-001400US) and 7,226,467(Attorney Docket No. 020489-001700US), the entire contents of each,fully incorporated herein by reference. One of skill in the art willappreciate that the various features of the disclosed fixation devicesmay be substituted with one another or used in combination with otherdisclosed features.

IV. Delivery Device

A. Overview of Delivery Device

FIG. 25 provides a perspective view of an embodiment of a deliverydevice or delivery catheter 300 which may be used to introduce andposition a fixation device as described above. The delivery catheter 300includes a shaft 302, having a proximal end 322 and a distal end 324,and a handle 304 attached to the proximal end 322. A fixation device(not shown) is removably coupleable to the distal end 324 for deliveryto a site within the body, typically for endovascular delivery to themitral valve. Thus, extending from the distal end 324 is a couplingstructure 320 for coupling with a fixation device. Also extending fromthe distal end 324 is an actuator rod 64. The actuator rod 64 isconnectable with the fixation device and acts to manipulate the fixationdevice, typically opening and closing the distal elements. Such couplingto a fixation device is illustrated in FIG. 26.

FIG. 26 illustrates an embodiment of a fixation device 14 coupled to thedistal end 324 of the delivery catheter 300. The shaft 302 is shownhaving a nose 318 near its distal end 324. In this embodiment, the nose318 has a flanged shape. Such a flanged shape prevents the nose 318 frombeing retracted into a guiding catheter or introducer as will bediscussed in later sections. However, it may be appreciated that thenose 318 may have any shape including bullet, rounded, blunt or pointed,to name a few. Extending from the nose 318 is a compression coil 326through which the coupling structure 320 and actuator rod 64 pass. Theactuator rod 64 is coupleable, as shown, with the stud 74 of thefixation device 14. Such coupling is illustrated in FIG. 27.

FIG. 27 illustrates a portion of the shaft 302 of the delivery catheter300 and a fixation device 14 which is coupleable with the catheter 300.Passing through the shaft 302 is the actuator rod 64. In thisembodiment, the actuator rod 64 comprises a proximal extremity 303 and adistal extremity 328, the distal extremity 328 of which is surrounded bya coil 330. The proximal extremity 303 is typically comprised ofstainless steel, nitinol, or Elgiloy®, to name a few, and may have adiameter in the range of 0.010 in. to 0.040 in., preferably 0.020 in. to0.030 in., more preferably 0.025 in., and a length in the range of 48 to72 in. The distal extremity 328 may be tapered, is typically comprisedof stainless steel, nitinol, or Elgiloy®, to name a few, and may have adiameter in the range of 0.011 to 0.025 in and a length in the range of4 to 12 in. Such narrowing increases flexibility of the distal end 324of the actuator rod 64. The actuator rod 64 further comprises a joiner332 which is attached to the distal extremity 328. The joiner 332 isremovably attachable with stud 74 of the fixation device 14. In thisembodiment, the joiner 332 has internal threads which mate with externalthreads on the stud 74 of the fixation device 14. As describedpreviously, the stud 74 is connected with the distal elements 18 so thatadvancement and retraction of the stud 74, by means of the actuator rod64, manipulates the distal elements. Likewise, the coupling member 19 ofthe fixation device 14 mates with the coupling structure 320 of thecatheter 300. Thus, the coupling member 19 and coupling structure 320function as previously described in relation to FIGS. 6A-6B.

Referring back to FIG. 26, the fixation device 14 may also include alocking mechanism which includes a release harness 108, as previouslydescribed in relation to FIGS. 17-20. Lock lines 92 are connected withthe release harness 108 to lock and unlock the locking mechanism 106 aspreviously described. The lock lines 92 extend through the shaft 302 ofthe delivery catheter 300 and may connect with the release harness 108in various arrangements as will be illustrated in later sections.Similarly, proximal element lines 90 extend through the shaft 302 of thedelivery catheter 300 and connect with the proximal elements 16. Theproximal elements 16 are raised and lowered by manipulation of theproximal element lines 90 as previously described. The proximal elementlines 90 may connect with the proximal elements 16 in variousarrangements as will be illustrated in later sections.

Referring back to FIG. 25, the handle 304 attached to the proximal end322 of the shaft 302 is used to manipulate the coupled fixation device14 and to optionally decouple the fixation device 14 for permanentimplantation. As described, the fixation device 14 is primarilymanipulated by the actuator rod 64, proximal element lines 90 and locklines 92. The actuator rod 64 manipulates the distal elements 18, theproximal element lines 90 manipulate the proximal elements 16 and thelock lines 92 manipulate the locking mechanism. In this embodiment, theactuator rod 64 may be translated (extended or retracted) to manipulatethe distal elements 18. This is achieved with the use of the actuatorrod control 314 which will be described in later sections. The actuatorrod 64 may also be rotated to engage or disengage the threaded joinerwith the threaded stud 74. This is achieved with the use of the actuatorrod handle 316 which will also be described in later sections. Further,the proximal element lines 90 may be extended, retracted, loaded withvarious amounts of tension or removed with the use of the proximalelement line handle 312. And, the lock lines 92 may be may be extended,retracted, loaded with various amounts of tension or removed with theuse of the lock line handle 310. Both of these handles 310, 312 will bedescribed in more detail in later sections. The actuator rod handle 316,actuator rod control 314, proximal element line handle 312 and lock linehandle 310 are all joined with a main body 308 within which the actuatorrod 64, proximal element lines 90 and lock lines 92 are guided into theshaft 302. The handle 304 further includes a support base 306 connectedwith the main body 308. The main body 308 is slideable along the supportbase 306 to provide translation of the shaft 302. Further, the main body308 is rotateable around the support base 306 to rotate the shaft.

While the embodiment of FIG. 27 is promising, in certain situations, theactuator rod 64 may deform, especially along the thinner distalextremity region 328, during delivery of fixation device 14, therebymaking it more challenging to properly deliver and attach the fixationdevice to the valve leaflets. For example, when tracking tortuousvessels, or when steering the distal portion of the delivery devicethrough large angles, e.g. 90° or more, the distal tapered extremity 328of the actuator rod 64 may take a permanent set and thus may fail toreturn to a substantially straight configuration after being deflected.FIGS. 28A-28B illustrate an alternative embodiment of the actuator rodillustrated in FIG. 27. In this embodiment, the distal tapered extremity328 has been replaced with a flexible cable. Actuator rod 64 a is a longshaft or mandrel that generally takes the same form as actuator rod 64in FIG. 27. A flexible cable 2702 is disposed between a distal end ofthe actuator rod 64 a, and a proximal end of coupler or joiner 2708. Theflexible cable 2702 allows torque, tension, and compression to betransmitted to the coupler 2708, while allowing bending and flexingwithout resulting in the flexible cable taking a set. In this exemplaryembodiment, a distal portion of actuator rod 64 a is joined to aproximal end of the flexible cable 2702 with a sleeve 2704. The sleeve2704 has a central channel 2718 extending therethrough for receiving theflexible cable and the actuator rod. The sleeve 2704 may then becrimped, swaged, or otherwise reduced in diameter in order to fixedlyattach the two ends together. In alternative embodiments, adhesives,welds, soldering joints, etc. may also be used to join the two endstogether. Similarly, a proximal end of the coupler 2708 may include acentral channel 2718 that is sized to receive a distal portion of theflexible cable 2702. In this exemplary embodiment, the coupler iscylindrically shaped with a proximal portion 2716 having a largerdiameter than the distal portion 2710. After the proximal portion 2716has been crimped or swaged onto the flexible cable, the diameters of theproximal and distal portions of the coupler may be the same, asillustrated in FIG. 28B. The distal portion of the coupler may include athreaded channel 2712 which may be threadably attached to the fixationdevice 14, such as previously described above in FIGS. 7 and 27. FIG.28B illustrates the actuator rod 64 a after it has been coupled with theflexible cable and the coupler by swaging.

The flexible cable is preferably resiliently biased to return to asubstantially straight or linear configuration, even after being bent ordeflected by 90° or more. In preferred embodiments, the flexible cableis 25 cm or shorter, preferably 10 cm to 20 cm long, and more preferably15 to 20 cm long. The flexible cable also has an outer diameterpreferably 0.015″ to 0.035″ and more preferably is 0.020″ to 0.030″ andnominally is 0.025″ although one of skill in the art will appreciatethat other dimensions may also be used. The actuator rod 64 a generallytakes the same form as actuator rod 64 in FIG. 27. The actuator rod 64 aand flexible cable 2702 are configured to transmit at least 0.74inch-ounces of torque with a substantially 1:1 torque transmission ratiofrom the proximal end of the actuator mandrel to the distal end of theflexible cable. This torque is required to threadably disengage thecoupler 2708 from the fixation device after the valve has beensatisfactorily repaired. Additionally, the actuator rod 64 a and theflexible cable 2702 are also designed to transmit at least 2.5 pounds ofcompressive force distally to the fixation device in order to actuatethe distal elements thereof. Also, the actuator rod and flexible cablecan withstand at least 14.7 pounds of tensile force without substantialstretching or elongation. This force is experienced when actuating thefixation device to close the distal elements. Various metals, polymers,and other materials may be used for the actuator rod, flexible cable,sleeve, and coupler. However, in preferred embodiments, the coupler isfabricated from 17-4 H1150 stainless steel, while the cable comprises304V stainless steel, and the mandrel is 304 stainless steel with anultraspring wire temper.

Various configurations of the flexible cable may be used, such as thecable illustrated in FIGS. 29A-32B. The flexible cable of FIG. 29A-32Bis a stranded cable with a reverse wind designed to have a high torquetransmission ratio in the counterclockwise direction. This cableincludes four layers of wires. The innermost layer 2802 is seen in FIG.29A and includes three wires 2802 a, 2802 b, 2802 c helically woundtogether. FIG. 29B illustrates a cross-section of cable 2802 taken alongthe line A-A. The next layer 2902 comprises nine additional strands ofwire 2904 wrapped around the innermost layer 2802 as illustrated in FIG.30A. FIG. 30B is a cross-section taken along the line B-B. The nextlayer 3002 is illustrated in FIG. 31A, and comprises ten additionalstrands of wire 3006 wrapped around layer 2902, and a cross-sectiontaken along line D-D is shown in FIG. 31B. Finally, the outermost layer3102 comprises ten more wires 3108 wrapped around layer 3002 as seen inFIG. 32A, with cross-sectional taken along line D-D in FIG. 32B. One ofskill in the art will appreciate the various strand materialcharacteristics (e.g. diameter, tensile strength, etc.) and windingpatterns that may be used.

An alternative embodiment is illustrated in FIGS. 33A-37B. Thisembodiment is similar to that previously described above, with the majordifference being that after the cable has been wound, it is drawnthereby altering the surface finish and some of the mechanicalcharacteristics. FIG. 33A illustrates the innermost layer 3202 whichincludes three wires 3204 wound together, as seen in the cross-sectionof FIG. 33B taken along the line A-A. FIG. 34A shows the next layer 3302which includes nine wires 3304 wrapped around the innermost layer 3202.FIG. 34B shows a cross-section taken along line B-B. The next layer 3402of wires are shown in FIG. 35A having ten wires 3404 wrapped around theprevious layer 3302, as illustrated in the cross-section of FIG. 35Btaken along line C-C. The outermost layer 3502 is shown in FIG. 36A andincludes another ten wires 3504 wrapped around the previous layer 3402,with cross-section taken along line D-D in FIG. 36B. The assembly offour layers of wire are then drawn in order to alter the surface finishof the cable and to alter material properties of the finished cableassembly to a desired value. FIG. 37A illustrates the finished cableassembly 3602 with cross-section taken along line E-E in FIG. 37B. Oneof skill in the art will appreciate that other cable configurations maybe used, and that these are only exemplary embodiments.

B. Delivery Catheter Shaft

FIG. 38 illustrates a cross-sectional view of the delivery cathetershaft 302 of FIG. 25. In this embodiment, the shaft 302 has a tubularshape with inner lumen 348 and is comprised of a material which provideshoop strength while maintaining flexibility and kink resistance, such asa braided laminated material. Such material may include stainless steelbraided or coiled wire embedded in a polymer such as polyurethane,polyester, Pebax, Grilamid TR55, and AESNO to name a few. To providefurther support and hoop strength, a support coil 346 is disposed withinthe lumen 348 of shaft 302 as illustrated in FIG. 38.

Passing through the support coil 346 are a variety of elongated bodies,including tubular guides and cylindrical rods. For example, one type oftubular guide is a compression coil 326 extending through lumen 348 fromthe proximal end 322 to the distal end 324 of the shaft 302, and theactuator rod 64 extends through the compression coil 326. Therefore, thecompression coil typically has a length in the range of 48 to 60 in. andan inner diameter in the range of 0.020 to 0.035 in. to allow passage ofthe actuator rod 64 therethrough. The actuator rod 64 is manipulable torotate and translate within and relative to the compression coil 326.The compression coil 326 allows lateral flexibility of the actuator rod64 and therefore the shaft 302 while resisting buckling and providingcolumn strength under compression. The compression coil may be comprisedof 304V stainless steel to provide these properties.

To provide additional tensile strength for the shaft 302 and to minimizeelongation, a tension cable 344 may also pass through the support coil346. The tension cable 344 extends through lumen 348 from the proximalend 322 to the distal end 324 of the shaft 302. Therefore, the tensioncable 344 typically has a diameter in the range of 0.005 in. to 0.010in. and a length in the range of 48 to 60 in. In preferred embodiments,the tension cable 344 is comprised of 304V stainless steel.

In addition, at least one lock line shaft 341 having a tubular shape maybe present having a lock line lumen 340 through which lock lines 92 passbetween the lock line handle 310 and the locking mechanism 106. The lockline shaft 341 extends through lumen 348 from the proximal end 322 tothe distal end 324 of the shaft 302. Therefore, the lock line shaft 341typically has a length in the range of 48 to 60 in., an inner diameterin the range of 0.016 to 0.030 in., and an outer diameter in the rangeof 0.018 to 0.034 in. In preferred embodiments, the lock line shaft 341is comprised of a 304V stainless steel coil however other structures ormaterials may be used which provide kink resistance and compressionstrength.

Similarly, at least one proximal element line shaft 343 having a tubularshape may be present having a proximal element line lumen 342. Proximalelement lines 90 pass through this lumen 342 between the proximalelement line handle 312 and the proximal elements 16. Thus, the proximalelement line shaft 343 extends through lumen 348 from the proximal end322 to the distal end 324 of the shaft 302. Therefore, the proximalelement line shaft 343 typically has a length in the range of 48 to 60in., an inner diameter in the range of 0.016 to 0.030 in., and an outerdiameter in the range of 0.018 to 0.034 in. In preferred embodiments,the proximal element line shaft 343 is comprised of a 304V stainlesssteel coil however other structures or materials may be used whichprovide kink resistance and compression strength.

In this embodiment, the elongated bodies (compression coil 326 enclosedactuator rod 64, tension cable 344, lock line shaft 342, proximalelement line shaft 343) each “float” freely in inner lumen 348 withinthe support coil 346 and are fixed only at the proximal end 322 anddistal end 324 of shaft 302. The lumen 348 is typically filled andflushed with heparinized saline during use. Alternatively or inaddition, the lumen 348 may be filled with one or more fillers, such asflexible rods, beads, extruded sections, gels or other fluids.Preferably the fillers allow for some lateral movement or deflection ofthe elongated bodies within lumen 348 but in some cases may restrictsuch movement. Typically, the elongated bodies are fixed at the proximaland distal ends of the shaft and are free to move laterally androtationally therebetween. Such freedom of movement of the elongatedbodies provides the shaft 302 with an increased flexibility as theelongated bodies self-adjust and reposition during bending and/ortorqueing of the shaft 302. It may be appreciated that the elongatedbodies may not be fixed at the proximal and distal ends. The elongatedbodies are simply unconstrained relative to the shaft 302 in at leastone location so as to be laterally moveable within the lumen 348.Preferably the elongated bodies are unrestrained in at least a distalportion of the catheter, e.g. 5-15 cm from the distal end 324, so as toprovide maximum flexibility in the distal portion.

It may be appreciated, however, that alternate shaft 302 designs mayalso be used. For example, referring to FIG. 39, in this embodiment theshaft 302 again has a tubular shape with an inner lumen 348 and asupport coil 346 disposed within the lumen 348 of shaft 302. Filling theinner lumen 348 within the support coil 346 is an extrusion 334 havinglumens through which pass a variety of elongated bodies, including thecompression coil 326 enclosed actuator rod 64, tension cable 344, lockline shafts 342, and proximal element line shafts 343, as shown. Thesupport coil 346 and elongated bodies may have the same geometries andbe comprised of the same materials as described above in relation toFIG. 38.

Alternatively, as shown in FIG. 40, the shaft 302 may include aninternal partition 350 to create multiple lumens within the shaft 302.For example, the partition 350 may have a central lumen 352 for passageof the actuator rod 64, optionally surrounded by the compression coil326. In addition, the partition 350 may also create at least one lockline lumen 340 for passage of a lock line 92 and at least one proximalelement line lumen 341 for passage of a proximal element line 90.Optionally, each of the lumens defined by partition 350 may be linedwith a kink-resistant element, such as a coil as in previousembodiments.

FIGS. 40A-40B illustrate embodiments of the nose 318 of the shaft 302.In FIG. 40A, the nose 318 comprises a tip ring 280 and a lock ring 282.In preferred embodiments, Epoxy and PEBAX are deposited between the tipring 280 and the lock ring 282 to bond them together. The lock ring 282has a geometry to mate with the tip ring 280 to maintain relativealignment between the two. FIG. 40B illustrates another embodiment ofthe nose 318 of the shaft 302. Here, the tip ring 280 is covered by asoft tip 284 to provide a more atraumatic tip and a smoother transitionto the shaft.

C. Lock Line Arrangements

As mentioned previously, when lock lines 92 are present, the lines 92pass through at least one lock line lumen 340 between the lock linehandle 310 and the locking mechanism 106. The lock lines 92 engage therelease harnesses 108 of the locking mechanism 106 to lock and unlockthe locking mechanism 106 as previously described. The lock lines 92 mayengage the release harnesses 108 in various arrangements, examples ofwhich are illustrated in FIGS. 41A-41C. In each embodiment, two lockline lumens 340 are present within the shaft 302 of the deliverycatheter 300 terminating at the nose 318. The lumens 340 are disposed onalternate sides of the actuator rod 64 so that each lumen 340 isdirected toward a release harness 108.

FIG. 41A illustrates an embodiment wherein two lock lines 92, 92′ passthrough a single lock line lumen 340 and are threaded through a releaseharness 108 on one side of the actuator rod 64 (the actuator rod 64 isshown without surrounding housing such as coupling structure, forclarity). The lock lines 92, 92′ are then separated so that each lockline passes on an opposite side of the actuator rod 64. The lock lines92, 92′ then pass through the release harness 108′ on the opposite sideof the actuator rod 64 and continue together passing through a anothersingle lock line lumen 340′. This lock line arrangement is the samearrangement illustrated in FIG. 26.

FIG. 41B illustrates an embodiment wherein one lock line 92 passesthrough a single lock line lumen 340, is threaded through a releaseharness 108 on one side of the actuator rod 64, and is returned to thelock line lumen 340. Similarly, another lock line 92′ passes throughanother single lock line lumen 340′, is threaded through a differentrelease harness 108′ located on the opposite side of the actuator rod64, and is returned to the another single lock line lumen 340′.

FIG. 41C illustrates an embodiment wherein both lock lines 92, 92′ passthrough a single lock line lumen 340. One lock line 92 is threadedthrough a release harness 108 on one side of the actuator rod 64 and isthen passed through another lock line lumen 340′ on the opposite side ofthe actuator rod 64. The other lock line 92′ is threaded through anotherrelease harness 108′ on the other side of the actuator rod 64′ and isthen passed through the another lock line lumen 340′ with the previouslock line 92.

It may be appreciated that a variety of lock line arrangements may beused and are not limited to the arrangements illustrated and describedabove. The various arrangements allow the harnesses 108 to bemanipulated independently or jointly, allow various amounts of tensionto be applied and vary the force required for removal of the lock lineswhen the fixation device is to be left behind. For example, a singlelock line passing through one or two lumens may be connected to bothrelease harnesses for simultaneous application of tension.

D. Proximal Element Line Arrangements

As mentioned previously, when proximal element lines 90 are present, thelines 90 pass through at least one proximal element line lumen 342between the proximal element line handle 312 and at least one proximalelement 16. The proximal element lines 90 engage the proximal elements16 to raise or lower the element 16 as previously described. Theproximal element lines 90 may engage the proximal elements 16 in variousarrangements, examples of which are illustrated in FIGS. 42A-42B. Ineach embodiment, two proximal element line lumens 342 are present withinthe shaft 302 of the delivery catheter 300 terminating at the nose 318.The lumens 342 are disposed on alternate sides of the actuator rod 64(the actuator rod 64 is shown without surrounding housing such ascoupling structure, for clarity) so that each lumen 342 is directedtoward a proximal element 16.

FIG. 42A illustrates an embodiment wherein one proximal element line 90passes through a single proximal element line lumen 342. The proximalelement line 90 is threaded through an eyelet 360 of a proximal element16 on one side of the actuator rod 64, passes over the actuator rod 64and is threaded through an eyelet 360′ of another proximal element 16′on the other side of the actuator rod 64. The proximal element line 90then passes through another single proximal element line lumen 342′.This proximal element line arrangement is the same arrangementillustrated in FIG. 26.

FIG. 42B illustrates an embodiment wherein one proximal element line 90passes through a single proximal element line lumen 342, is threadedthrough an eyelet 360 of a proximal element 16 on one side of theactuator rod 64, and is returned to the proximal element line lumen 342.Similarly, another proximal element line 90′ passes through anothersingle proximal element line lumen 342′ on the opposite side of theactuator rod 64, and is returned to the another single proximal elementline lumen 342′.

It may be appreciated that a variety of proximal element linearrangements may be used and are not limited to the arrangementsillustrated and described above. The various arrangements allow theproximal elements to be manipulated independently or jointly, allowvarious amounts of tension to be applied and vary the force required forremoval of the proximal element lines when the fixation device is to beleft behind. For example, a single proximal element line passing throughone or two lumens in shaft 302 may be used for simultaneous actuation ofboth proximal elements.

E. Main Body of Handle

FIG. 43 illustrates an embodiment of the handle 304 of the deliverycatheter 300. As mentioned previously, the actuator rod handle 316,actuator rod control 314, proximal element line handle 312 and lock linehandle 310 are all joined with the main body 318. The handle 304 furtherincludes a support base 306 connected with the main body 308. The mainbody 308 is slideable along the support base 306 to provide translationof the shaft 302 and the main body 308 is rotateable around the supportbase 306 to rotate the shaft.

FIG. 44 provides a partial cross-sectional view of the main body 308 ofthe handle 304 depicted in FIG. 43. As shown, the main body 308 includesa sealed chamber 370 within which the actuator rod 64, proximal elementlines 90 and lock lines 92 are guided into the shaft 302. The sealedchamber 370 is in fluid communication with the inner lumen 348 of shaft302 and is typically filled with saline and flushed with heparin orheparinized saline. The sealed chamber 370 has a seal 372 along itsperimeter to prevent leakage and the introduction of air to the chamber370. Any air in the chamber 370 may be bled from the chamber 370 by oneor more luers 374 which pass through the main body 308 into the chamber370 as illustrated in FIG. 43. In this embodiment, the handle 304includes two such luers 374, one on each side of the main body 308(second luer symmetrically positioned on backside of main body 308 inFIG. 43, hidden from view). Referring now to FIG. 44, the sealed chamber370 also has various additional seals, such as an actuator rod seal 376which surrounds the actuator rod 64 where the actuator rod 64 enters thesealed chamber 370, and a shaft seal 378 which surrounds the shaft 302where the shaft 302 enters the sealed chamber 370.

F. Lock Line Handle and Proximal Element Line Handle

As mentioned previously, the lock lines 92 may be may be extended,retracted, loaded with various amounts of tension or removed using thelock line handle 310. Likewise, the proximal element lines 90 may beextended, retracted, loaded with various amounts of tension or removedusing the proximal element line handle 312. Both of these handles 310,312 may be similarly designed to manipulate the appropriate lines 90, 92passing therethrough.

FIG. 45 illustrates an embodiment of a lock line handle 310 having locklines 92 passing therethrough. The lock line handle 310 has a distal end384, a proximal end 382 and an elongate shaft 383 therebetween. Thedistal end 382 is positionable within the sealed chamber 370 so that theproximal end 382 extends out of the chamber 370, beyond the main body308. The free ends of the lock lines 92 are disposed near the proximalend 382, passing through the wall of the handle 310 near a threaded nub390. The handle 310 further includes a cap 388 which is positionable onthe nub 309. Internal threading with the cap 388 mates with thethreading on the threaded nub 390 so that the cap 388 holds the freeends of the lock lines 92 between the cap 388 and the nub 390 and/orother portions of the handle 310 by friction. The lock lines 92 passthrough a central lumen (not shown) of the elongate shaft 383, extendthrough the sealed chamber 370 (as shown in FIG. 44) and extend throughthe shaft 302 to the locking mechanism 106.

Disposed near the distal end 384 of the handle 310 is at least one wing392. In the embodiment of FIG. 45, two wings 392 are present, each wing392 disposed on opposite sides of the elongate shaft 383. The wings 392extend radially outwardly and curve proximally so that a portion isparallel to the elongate shaft 383, as shown. It may be appreciated thatthe wings 392 may alternatively have the shape of solid or continuousprotrusions which extend radially and have a portion which is parallelto the elongate shaft 383. The wings 392 are used to hold the lock linehandle 310 in a desired position which in turn holds the lock under adesired load of tension, as will be described further below. The handle310 also includes a finger grip 386 near the proximal end 382 whichextends radially outwardly in alignment with the radial extension of theat least one wing 392. Thus, the user may determine the orientation ofthe wings 392 within the sealed chamber 370 from the orientation of thefinger grip 386 outside of the main body 308. The finger grip 386 mayalso serve an ergonomic purpose to assist in manipulating the handle310.

The portion of the wings 392 parallel to the elongate shaft 383 havegrooves or serrations 394. The serrations 394 are used to apply tensionto the lock lines 92. As shown in FIG. 45A, the lock line handle 310 ispositioned within a semi-tube 400 which is disposed within the sealedchamber 370. The semi-tube 400 comprises a top half 402 and a bottomhalf 404, each half 402, 404 having grooves or serrations 406 which matewith the serrations 394 of the wings 392. Thus, when the wings 392 arerotated to mate the serrations 394, 406, as shown in FIG. 46A, theelongate shaft 383 is held in place. Likewise, the wings 392 may berotated, as shown in FIG. 46B, so that the wings 392 are disposedbetween the halves 402, 404 and the serrations 394, 406 are disengaged.In this position, the shaft 383 may be translated to apply or releasetension in the lock lines 92. Thus, tension in the lines 92 may beadjusted by rotating the shaft 383 to disengage the serrations 394, 406,translating the shaft 383 and then rotating the shaft 383 back toreengage the serrations 394, 406. Alternatively, the finger grip 386 maybe pulled to apply tension to the lock lines 92. Pulling the finger grip386 translates the lock line handle 310 within the semi-tube 400. Suchtranslation is achievable due to angling of the serrations 394, 406 andflexibility of wings 382. However, the angling of the serrations 394,406 prevents translation in the opposite direction, i.e. by pushing thefinger grip 386. Therefore, to release tension from the lock lines 92,the shaft 383 is rotated to disengage the serrations 394, 406, allowingtranslation of the shaft 383, and then the shaft 383 is rotated back toreengage the serrations 394, 406.

To remove the lock lines 92, the cap 388 is removed from the threadednub 390 exposing the free ends of the lock lines 92. If one lock line 92is present having two free ends, continuous pulling on one of the freeends draws the entire length of lock line 92 out of the catheter 300. Ifmore than one lock line 92 is present, each lock line 92 will have twofree ends. Continuous pulling on one of the free ends of each lock line92 draws the entire length of each lock line 92 out of the catheter 300.

It may be appreciated that the proximal element line handle 312 hascorresponding features to the lock line handle 310 and operates in thesame manner as illustrated in FIGS. 45A, 46A-46B. It may also beappreciated that other mechanisms may be used for manipulating the locklines 92 and proximal element lines 90, such as including buttons,springs, levers and knobs.

G. Actuator Rod Control and Handle

The actuator rod 64 may be manipulated using the actuator rod control314 and the actuator rod handle 316. FIG. 47 provides a cross-sectionalview of a portion of the handle 304 which includes the actuator rodcontrol 314 and the actuator rod handle 316. The actuator rod handle 316is located at the proximal end of the handle 314. The actuator rodhandle 316 is fixedly attached to the proximal end of the actuator rod64. The actuator rod 64 is inserted through a collet 426 which isdisposed within a holder 428 as shown. The holder 428 has externalthreads 434 which mate with internal threads 432 of the actuator rodcontrol 314. Thus, rotation of the actuator rod control 314 causes theholder 428 to translate along the actuator rod control 314 by action ofthe threading, as will be described in more detail below. The actuatorrod control 314 is rotatably coupled with the main body 308 of thehandle 304 and is held in place by a lip 430.

Referring to FIG. 47A, the actuator rod control 314 may be manuallyrotated in a clockwise or counter clockwise direction, as indicated byarrow 436. Rotation of the actuator rod control 314 translates (extendsor retracts) the actuator rod 64 to manipulate the distal elements 18 ofthe fixation device 14. Specifically, rotation of the actuator rodcontrol 314 causes the external threads 434 of the adjacent holder 428to translate along the mated internal threads 432 of the actuator rodcontrol 314. Rotation of the holder 428 itself is prevented by holdingpins 424 which protrude from the holder 428 and nest into grooves 438 inthe main body 308 of the handle 304. As the holder 428 translates, eachholding pin 424 translates along its corresponding groove 438. Since thecollet 426 is attached to the holder 428, the collet 426 translatesalong with the holder 428. To simultaneously translate the actuator rod64, the actuator rod 64 is removably attached to the collet 426 by a pin422. The pin 422 may have any suitable form, including a clip-shapewhich partially wraps around the collet 426 as illustrated in FIG. 47.Thus, rotation of the actuator rod control 314 provides fine control oftranslation of the actuator rod 64 and therefore fine control ofpositioning the distal elements 18.

Referring to FIG. 47B, removal of the pin 422, as shown, allowsdisengagement of the actuator rod handle 316 and fixedly attachedactuator rod 64 from the collet 426. Once disengaged, the actuator rod64 may be rotated, as indicated by arrow 440, by manually rotating theactuator rod handle 316. As described previously, rotation of theactuator rod 64 engages or disengages the threaded joiner 332 of thedelivery catheter 300 from the threaded stud 74 of the fixation device14. This is used to attach or detach the fixation device 14 from thedelivery catheter 300. In addition, when the actuator rod 64 is in thedisengaged state, the actuator rod 64 may optionally be retracted andoptionally removed from the catheter 300 by pulling the actuator rodhandle 316 and withdrawing the actuator rod 64 from the handle 304.

Depending on the application, the location of the target site, and theapproach selected, the devices of the invention may be modified in wayswell known to those of skill in the art or used in conjunction withother devices that are known in the art. For example, the deliverycatheter may be modified in length, stiffness, shape and steerabilityfor a desired application. Likewise, the orientation of the fixationdevice relative to the delivery catheter may be reversed or otherwisechanged. The actuation mechanisms may be changed to be driven inalternate directions (push to open, pull to close, or pull to open, pushto close). Materials and designs may be changed to be, for example, moreflexible or more rigid. And the fixation device components may bealtered to those of different size or shape. Further, the deliverycatheter of the present invention may be used to deliver other types ofdevices, particularly endovascular and minimally invasive surgicaldevices used in angioplasty, atherectomy, stent-delivery, embolicfiltration and removal, septal defect repair, tissue approximation andrepair, vascular clamping and ligation, suturing, aneurysm repair,vascular occlusion, and electrophysiological mapping and ablation, toname a few. Thus, the delivery catheter of the present invention may beused for applications in which a highly flexible, kink-resistant deviceis desirable with high compressive, tensile and torsional strength.

H. Pusher Handle Design

After engaging successfully grasping the leaflets, usually at an anglebetween 120 and 180 degrees, the actuator rod 64 is manually rotated tomanipulate the distal elements of the fixation device. This moves thedistal elements proximally to an angle, such as 60 degrees as shown inFIG. 11B. However, with reference to FIG. 15B, the gripper pusher 81 andthe proximal element actuators 90 also need to be retracted as anglebetween the distal elements 18 is reduced. FIG. 70 shows an embodimentof a handle that coordinates these movements. As shown in the figure,the proximal element line handle 312 of FIG. 44 is fitted with a springloaded pusher attachment 414 that is connected to a gripper pusheractuator 411 that extends to the gripper pusher 81 of the fixationdevice. This spring loaded pusher attachment 414 surrounds, but movesindependently of the proximal element line 90. The spring 413 functionsto provide a tension on the proximal element line 90 by exerting a smallforce on the gripper pusher 81 relative to the gripper pusher actuator.Further, a gripper pusher actuator wire 412 is coupled to the actuatorrod 64 so that when the actuator rod 64 is actuated to close the distalelements 18, the gripper pusher 81 is retracted. As shown in FIG. 70,the pusher actuator wire 412 interacts with the spring loaded pusherattachment 414 to retract the spring loaded pusher attachment 414 whenthe distal elements 18 are closed. On the other hand, the distal end ofthe pusher actuator wire 412 is configured to slide distally withrespect to the spring loaded pusher attachment 414 so that the distalmovement of the gripper pusher 81 is independent of the movement of thedistal elements 18. This permits separation between the proximalelements 16 and the distal elements 18 to aid in grasping leaflets.Lastly, due to the spring coupling between the spring loaded pusherattachment 414 and the proximal element line handle 312, the proximalelement actuator 90 is also retracted in combination with the retractingof the gripper pusher actuator 411. Notably, due to the spring couplingvia the spring 413, the proximal element actuator 90 is permittedfurther travel than the gripper pusher actuator 411. This additionaltravel is permitted via expansion of the spring 413 and functions toremove slack in the proximal element actuator as the angle between theproximal elements 16 and the distal elements 18 is reduced.

V. Multi-Catheter Guiding System

A. Overview of Guiding System

Referring to FIG. 48, an embodiment of a multi-catheter guiding system 1of the present invention is illustrated. The system 1 comprises an outerguide catheter 1000, having a proximal end 1014, a distal end 1016, anda central lumen 1018 therethrough, and an inner guide catheter 1020,having a proximal end 1024, distal end 1026 and central lumen 1028therethrough, wherein the inner guide catheter 1020 is positionedcoaxially within the central lumen 1018 of the outer guide catheter1000, as shown. The distal ends 1016, 1026 of catheters 1000, 1020,respectively, are sized to be passable to a body cavity, typicallythrough a body lumen such as a vascular lumen. Thus, the distal end 1016preferably has an outer diameter in the range of approximately 0.040 in.to 0.500 in., more preferably in the range of 0.130 in. to 0.320 in. Thecentral lumen 1018 is sized for the passage of the inner guide catheter1020; the distal end 1026 preferably has an outer diameter in the rangeof approximately 0.035 in. to 0.280 in., more preferably 0.120 in to0.200 in. The central lumen 1028 is sized for the passage of a varietyof devices therethrough. Therefore, the central lumen 1028 preferablyhas an inner diameter in the range of approximately 0.026 in. to 0.450in., more preferably in the range of 0.100 in. to 0.180 in.

FIG. 48 illustrates an interventional catheter 1030 positioned withinthe inner guide catheter 1020 which may optionally be included in system1, however other interventional devices may be used. The interventionalcatheter 1030 has a proximal end 1034 and a distal end 1036, wherein aninterventional tool 1040 is positioned at the distal end 1036. In thisembodiment, the interventional tool 1040 comprises a detachable fixationdevice or clip. Optionally, the interventional catheter 1030 may alsoinclude a nosepiece 1042 having a stop 1043, as shown. The stop 1043prevents the interventional tool 1040 from entering the central lumen1028 of the inner guide catheter 1020. Thus, the interventional catheter1030 may be advanced and retracted until the stop 1043 contacts thedistal end 1026 of the inner guiding catheter 1020 preventing furtherretraction. This may provide certain advantages during some procedures.It may be appreciated that in embodiments which include such a stop1043, the interventional catheter 1030 would be pre-loaded within theinner guide catheter 1020 for advancement through the outer guidingcatheter 1000 or both the interventional catheter 1030 and the innerguiding catheter 1020 would be pre-loaded into the outer guidingcatheter 1000 for advancement to the target tissue. This is because thestop 1043 prevents advancement of the interventional catheter 1030through the inner guiding catheter 1020.

The outer guide catheter 1000 and/or the inner guide catheter 1020 areprecurved and/or have steering mechanisms, embodiments of which will bedescribed later in detail, to position the distal ends 1016, 1026 indesired directions. Precurvature or steering of the outer guide catheter1000 directs the distal end 1016 in a first direction to create aprimary curve while precurvature and/or steering of the inner guidecatheter 1020 directs distal end 1026 in a second direction, differingfrom the first, to create a secondary curve. Together, the primary andsecondary curves form a compound curve. Advancement of theinterventional catheter 1030 through the coaxial guide catheters 1000,1020 guides the interventional catheter 1030 through the compound curvetoward a desired direction, usually in a direction which will allow theinterventional catheter 1030 to reach its target.

Steering of the outer guide catheter 1000 and inner guide catheter 1020may be achieved by actuation of one or more steering mechanisms.Actuation of the steering mechanisms is achieved with the use ofactuators which are typically located on handles connected with each ofthe catheters 1000, 1020. As illustrated in FIG. 48, handle 1056 isconnected to the proximal end 1014 of the outer guide catheter 1000 andremains outside of the patient's body during use. Handle 1056 includessteering actuator 1050 which may be used to bend, arc or reshape theouter guide catheter 1000, such as to form a primary curve. Handle 1057is connected to the proximal end (not shown) of the inner guide catheter1020 and may optionally join with handle 1056 to form one larger handle,as shown. Handle 1057 includes steering actuator 1052 which may be usedto bend, arc or reshape the inner guide catheter 1020, such as to form asecondary curve and move the distal end 1026 of the inner guide catheter1020 through an angle theta, as will be described in a later section.

In addition, locking actuators 1058, 1060 may be used to actuate lockingmechanisms to lock the catheters 1000, 1020 in a particular position.Actuators 1050, 1052, 1058, 1060 are illustrated as buttons, however itmay be appreciated that these and any additional actuators located onthe handles 1056, 1057 may have any suitable form including knobs,thumbwheels, levers, switches, toggles, sensors or other devices. Otherembodiments of the handles will be described in detail in a latersection.

In addition, the handle 1056 may include a numerical or graphicaldisplay 1061 of information such as data indicating the position thecatheters 1000, 1020, or force on actuators. It may also be appreciatedthat actuators 1050, 1052, 1058, 1060 and any other buttons or screensmay be disposed on a single handle which connects with both thecatheters 1000, 1020.

B. Example Positions

FIGS. 49A-49D illustrate examples of positions that the catheters 1000,1020 may hold. Referring to FIG. 49A, the outer guide catheter 1000 maybe precurved and/or steered into a position which includes a primarycurve 1100. The primary curve 1100 typically has a radius of curvature1102 in the range of approximately 0.125 in. to 1.000 in., preferably inthe range of approximately 0.250 in. to 0.500 in. or forms a curve inthe range of approximately 0° to 120°. As shown, when the positionincludes only a primary curve 1100, the distal end 16 lies in a singleplane X. An axis x, transversing through the center of the central lumen18 at the distal end 16, lies within plane X.

Referring to FIG. 49B, the inner guide catheter 1020 extends through thecentral lumen 1018 of the outer guide catheter 1000. The inner guidecatheter 1020 may be precurved and/or steered into a position whichincludes a secondary curve 1104. The secondary curve 1104 typically hasa radius of curvature 10600 in the range of approximately 0.050 in. to0.750 in., preferably in the range of approximately 0.125 in. to 0.250in. or forms a curve in the range of approximately 0° to 180°. Thesecondary curve 1104 can lie in the same plane as the primary curve1100, plane X, or it can lie in a different plane, such as plane Z asshown. In this example, plane Z is substantially orthogonal to plane X.Axis z, transversing through the center of the central lumen 1028 of theinner guide catheter 1020 at the distal end 1026, lies within plane Z.In this example, axis x and axis z are at substantially 90 degree anglesto each other; however, it may be appreciated that axis x and axis z maybe at any angle in relation to each other. Also, although in thisexample the primary curve 1100 and the secondary curve 1104 lie indifferent planes, particularly in substantially orthogonal planes, thecurves 1100, 1104 may alternatively lie in the same plane.

Referring now to FIG. 49C, the inner guide catheter 1020 may be furthermanipulated to allow the distal end 1026 to move through an angle theta1070. The angle theta 1070 is in the range of approximately −180° to+180°, typically in the range of −90° to +90°, possibly in the range of−60° to +60°, −45° to +45°, −30° to +30° or less. As shown, the angletheta 1070 lies within a plane Y. In particular, axis y, which runsthrough the center of the central lumen 1028 at the distal end 1026,forms the angle theta 1070 with axis z. In this example, plane Y isorthogonal to both plane X and plane Z. Axes x, y, z all intercept at apoint within the central lumen 1028 which also coincides with theintersection of planes X, Y, Z.

Similarly, FIG. 49D illustrates movement of the distal end 1026 throughan angle theta 1070 on the opposite side of axis z. Again, the angletheta 1070 is measured from the axis z to the axis y, which runs throughthe center of the central lumen 1016 at the distal end 1026. As shown,the angle theta 1070 lies in plane Y. Thus, the primary curve 1100,secondary curve 1104, and angle theta 1070 can all lie in differentplanes, and optionally in orthogonal planes. However, it may beappreciated that the planes within which the primary curve 1100,secondary curve 1104 and angle theta 1070 lie may be mutually dependentand therefore would allow the possibility that some of these lie withinthe same plane.

In addition, the outer guide catheter 1000 may be pre-formed and/orsteerable to provide additional curves or shapes. For example, asillustrated in FIG. 50A, an additional curve 1110 may be formed by theouter guide catheter 1000 proximal to the primary curve 1100. In thisexample, the curve 1110 provides lift or raises the distal end 1016 ofthe outer guide catheter 1000, which in turn raises the distal end 1026of the inner guide catheter 1020. Such lifting is illustrated in FIG.50B. Here, the system 1 is shown prior to lifting in dashed line whereinthe axis y′ passes through the intersection of axis z and axis x′. Afterapplication of curve 1110, the distal portion of the system 1 is liftedin the direction of axis z so that axis x′ is raised to axis x″ and axisy′ is raised to axis y″. This raises distal end 1026 to a desiredheight.

The articulated position of the multi-catheter guiding system 1illustrated in FIGS. 49A-49D and FIGS. 50A-50B is particularly usefulfor accessing the mitral valve. FIGS. 51A-51D illustrate a method ofusing the system 1 for accessing the mitral valve MV. To gain access tothe mitral valve, the outer guide catheter 1000 may be tracked over adilator and guidewire from a puncture in the femoral vein, through theinferior vena cava and into the right atrium. As shown in FIG. 51A, theouter guide catheter 1000 may be punctured through a fossa F in theinteratrial septum S. The outer guide catheter 1000 is then advancedthrough the fossa F and curved by the primary curve 1100 so that thedistal end 1016 is directed over the mitral valve MV. Again, it may beappreciated that this approach serves merely as an example and otherapproaches may be used, such as through the jugular vein, femoralartery, port access or direct access, to name a few. Positioning of thedistal end 1016 over the mitral valve MV may be accomplished byprecurvature of the outer guide catheter 1000, wherein the catheter 1000assumes this position when the dilator and guidewire are retracted,and/or by steering of the outer guide catheter 1000 to the desiredposition. In this example, formation of the primary curve 1100 moves thedistal end 1016 within a primary plane, corresponding to previous planeX, substantially parallel to the valve surface. This moves the distalend 1016 laterally along the short axis of the mitral valve MV, andallows the distal end 1016 to be centered over the opening O between theleaflets LF.

Referring to FIG. 51B, the inner guide catheter 1020 is advanced throughthe central lumen 1018 of the outer guide catheter 1000 and the distalend 1026 is positioned so that the central lumen 1028 is directed towardthe target tissue, the mitral valve MV. In particular, the central lumen1028 is to be directed toward a specific area of the mitral valve MV,such as toward the opening O between the valve leaflets LF, so that aparticular interventional procedure may be performed. In FIG. 51B, theinner guide catheter 1020 is shown in a position which includes asecondary curve 1104 in a secondary plane, corresponding to previousplane Z. Formation of the secondary curve 1104 moves the distal end 1026vertically and angularly between the commissures C, directing thecentral lumen 1028 toward the mitral valve MV. In this position aninterventional device or catheter 1030 which is passed through thecentral lumen 1028 would be directed toward and/or through the openingO. Although the primary curve 1100 and the secondary curve 1104 may bevaried to accommodate different anatomical variations of the valve MVand different surgical procedures, further adjustment may be desiredbeyond these two curvatures for proper positioning of the system 1.

Referring to FIG. 51C, the distal end 1026 of the inner guide catheter1020 may be positioned through an angle theta 1070. This moves thedistal end 1026 vertically and angularly through a theta plane,corresponding to previous plane Y. Movement of the distal end 1026through the angle theta 1070 in either direction is shown in dashed linein FIG. 51C. Such movement can be achieved by precurvature and/or bysteering of the catheter 1020. Consequently, the central lumen 1028 canbe directed toward the mitral valve MV within a plane which differs fromthe secondary plane. After such movements, the inner guide catheter 1020will be in a position so that the opening of the central lumen 1028 atthe end 1016 faces the desired direction. In this case, the desireddirection is toward the center of and orthogonal to the mitral valve.

In some instances, it is desired to raise or lower the distal end 1026so that it is at a desired height in relation to the mitral valve MV.This may be accomplished by precurvature and/or by steering of the outerguide catheter 1000 to form additional curve 1110. Generally this isused to lift the distal end 1026 above the mitral MV wherein suchlifting was illustrated in FIG. 50B.

When the curvatures in the catheters 1000, 1020 are formed by steeringmechanisms, the steering mechanisms may be locked in place by a lockingfeature. Locking can provide additional stiffness and stability in theguiding system 1 for the passage of interventional devices or catheters1030 therethrough, as illustrated in FIG. 48. The interventionalcatheter 1030 can be passed through the central lumen 1028 toward thetarget tissue, in this case the mitral valve MV. Positioning of thedistal end 1026 over the opening O, as described above, allows thecatheter 1030 to pass through the opening O between the leaflets LF ifdesired, as shown in FIG. 51D. At this point, any desired procedure maybe applied to the mitral valve for correction of regurgitation or anyother disorder.

C. Steering Mechanisms

As described previously, the curvatures may be formed in the catheters1000, 1020 by precurving, steering or any suitable means. Precurvinginvolves setting a specific curvature in the catheter prior to usage,such as by heat setting a polymer or by utilizing a shape-memory alloy.Since the catheters are generally flexible, loading of the catheter on aguidewire, dilator obturator or other introductory device straightensthe catheter throughout the curved region. Once the catheter ispositioned in the anatomy, the introductory device is removed and thecatheter is allowed to relax back into the precurved setting.

To provide a higher degree of control and variety of possiblecurvatures, steering mechanisms may be used to create the curvatures andposition the catheters. In some embodiments, the steering mechanismscomprise cables or pullwires within the wall of the catheter. As shownin FIG. 52A, the outer guide catheter 1000 may include a pullwire 1120slidably disposed in lumens within the wall of the catheter 1000extending to the distal end 1016. By applying tension to the pullwire1120 in the proximal direction, the distal end 1016 curves in thedirection of the pullwire 1120 as illustrated by arrow 1122. Likewise,as shown in FIG. 52B, placement of the pullwire 1120 along the oppositeside of the catheter 1000 will allow the distal end 1016 to curve in theopposite direction, as illustrated by arrow 1124, when tension isapplied to the pullwire 1120. Thus, referring to FIG. 52C, diametricallyopposing placement of pullwires 1120 within the walls of the catheter1000 allows the distal end 1016 to be steered in opposite directions.This provides a means of correcting or adjusting a curvature. Forexample, if tension is applied to one pullwire to create a curvature,the curvature may be lessened by applying tension to the diametricallyopposite pullwire. Referring now to FIG. 52D, an additional set ofopposing pullwires 1120′ may extend within the wall of the catheter 1000as shown. This combination of pullwires 1120, 1120′ allows curvature ofthe distal end in at least four directions illustrated by arrows 1122,1124, 1126, 1128. In this example, pullwires 1120 create the primarycurve 1100 of the outer guide catheter 1000 and the pullwires 1120′create the lift. It may be appreciated that FIGS. 52A-52D also pertainto the inner guide catheter 1020. For example, in FIG. 52D, pullwires1120 may create the secondary curve 1104 of the inner guide catheter1020 and the pullwires 1120′ create the angle theta 1070.

Such pullwires 1120 and/or pullwires 1120′ and associated lumens may beplaced in any arrangement, singly or in pairs, symmetrically ornonsymmetrically and any number of pullwires may be present. This mayallow curvature in any direction and about various axes. The pullwires1120, 1120′ may be fixed at any location along the length of thecatheter by any suitable method, such as gluing, tying, soldering, orpotting, to name a few. When tension is applied to the pullwire, thecurvature forms from the point of attachment of the pullwire toward theproximal direction. Therefore, curvatures may be formed throughout thelength of the catheter depending upon the locations of the points ofattachment of the pullwires. Typically, however, the pullwires will beattached near the distal end of the catheter, optionally to an embeddedtip ring 280, illustrated in FIG. 52E. As shown, the pullwire 1120passes through an orifice 286 in the tip ring 280, forms a loop shapeand then passes back through the orifice 286 and travels back up throughthe catheter wall (not shown). In addition, the lumens which house thepullwires may be straight, as shown in FIGS. 52A-52D, or may be curved.

D. Catheter Construction

The outer guide catheter 1000 and inner guide catheter 1020 may have thesame or different construction which may include any suitable materialor combination of materials to create the above described curvatures.For clarity, the examples provided will be in reference to the outerguide catheter 1000, however it may be appreciated that such examplesmay also apply to the inner guide catheter 1020.

In embodiments in which the catheter is precurved rather than steerableor in addition to being steerable, the catheter 1000 may be comprised ofa polymer or copolymer which is able to be set in a desired curvature,such as by heat setting. Likewise, the catheter 1000 may be comprised ofa shape-memory alloy.

In embodiments in which the catheter is steerable, the catheter 1000 maybe comprised of one or more of a variety of materials, either along thelength of the catheter 1000 or in various segments. Example materialsinclude polyurethane, Pebax, nylon, polyester, polyethylene, polyimide,polyethylenetelephthalate(PET), polyetheretherketone (PEEK). Inaddition, the walls of the catheter 1000 may be reinforced with avariety of structures, such as metal braids or coils. Suchreinforcements may be along the length of the catheter 1000 or invarious segments.

For example, referring to FIG. 53A, the catheter 1000 may have aproximal braided segment 1150, a coiled segment 1152 and distal braidedsegment 1154. The proximal braided segment 1150 provides increasedcolumn strength and torque transmission. The coiled segment 1152provides increased steerability. The distal braided segment 1154provides a blend of steerability and torque/column strength. In anotherexample, referring to FIG. 53B, the outer guiding catheter 1000 has aproximal double-layer braided segment 1151 and a distal braided segment1154. Thus, the proximal double-layer segment 1151 comprises amulti-lumen tube 1160 (having steering lumens 1162 for pullwires, distalends of the steering lumens 1162 optionally embedded with stainlesssteel coils for reinforcement, and a central lumen 1163), an innerbraided layer 1164, and an outer braided layer 1166, as illustrated inthe cross-sectional view of FIG. 53C. Similarly, FIG. 53D provides across-sectional view of the distal braided segment 1154 comprising themulti-lumen tube 1160 and a single braided layer 1168. In a furtherexample, referring to FIG. 53E, the inner guiding catheter 1020comprises a multi-lumen tube 1160 without reinforcement at its proximalend, a single braided layer middle segment 1170 and a single braidedlayer distal segment 1171. Each of the single braided layer segments1170, 1171 have a multi-lumen tube 1160 and a single layer of braiding1168, as illustrated in cross-sectional view FIG. 53F. However, thesegments 1170, 1171 are comprised of polymers of differing durometers,typically decreasing toward the distal end.

FIG. 53G illustrates an other example of a cross-section of a distalsection of an outer guiding catheter 1000. Here, layer 1130 comprises55D Pebax and has a thickness of approximately 0.0125 in. Layer 1131comprises a 30 ppi braid and has a thickness of approximately 0.002 in.by 0.0065 in. Layer 1132 comprises 55D Pebax and has a thickness ofapproximately 0.006 in. Layer 1133 comprises 30 ppi braid and has athickness of approximately 0.002 in by 0.0065 in. And finally, layer1134 comprises Nylon 11 and includes steering lumens for approximately0.0105 in. diameter pullwires 1120. Central lumen 1163 is of sufficientsize for passage of devices.

FIGS. 53H-53I illustrate additional examples of cross-sections of aninner guiding catheter 1020, FIG. 53I illustrating a cross-section of aportion of the distal end and FIG. 53I illustrating a cross-section of amore distal portion of the distal end. Referring to FIG. 53H, layer 1135comprises 40D polymer and has a thickness of approximately 0.0125 in.Layer 1136 comprises a 30 ppi braid and has a thickness of approximately0.002 in. by 0.0065 in. Layer 1137 comprises 40D polymer and has athickness of approximately 0.006 in. Layer 1138 comprises a 40 D polymerlayer and has a thickness of approximately 0.0035 in. And finally, layer1139 comprises a 55D liner. In addition, coiled steering lumens areincluded for approximately 0.0105 in. diameter pullwires 1120. And,central lumen 1163 is of sufficient size for passage of devices.Referring to FIG. 53I, layer 1140 comprises a 40D polymer, layer 1141comprises a 35D polymer, layer 1142 comprises a braid and layer 1143comprises a liner. In addition, coiled steering lumens 1144 are includedfor pullwires. And, central lumen 1163 is of sufficient size for passageof devices.

FIGS. 54A-54C illustrate an embodiment of a keying feature which may beincorporated into the catheter shafts. The keying feature is used tomaintain relationship between the inner and outer guide catheters toassist in steering capabilities. As shown in FIG. 54A, the inner guidecatheter 1020 includes one or more protrusions 1400 which extendradially outwardly. In this example, four protrusions 1400 are present,equally spaced around the exterior of the catheter 1020. Likewise, theouter guide catheter 1000 includes corresponding notches 1402 whichalign with the protrusions 1400. Thus, in this example, the catheter1000 includes four notches equally spaced around its central lumen 1018.Thus, the inner guide catheter 1020 is able to be translated within theouter guide catheter 1000, however rotation of the inner guide catheter1020 within the outer guide catheter 1000 is prevented by the keyingfeature, i.e. the interlocking protrusions 1400 and notches 1402. Suchkeying helps maintain a known correlation of position between the innerguide catheter 1020 and outer guide catheter 1000. Since the inner andouter guide catheters 1020, 1000 form curvatures in differentdirections, such keying is beneficial to ensure that the compoundcurvature formed by the separate curvatures in the inner and outer guidecatheters 1020, 1000 is the compound curvature that is anticipated.Keying may also increase stability wherein the curvatures remain inposition reducing the possibility of compensating for each other.

FIG. 54B illustrates a cross-sectional view of the outer guidingcatheter 1000 of FIG. 54A. Here, the catheter 1000 includes a notchedlayer 1404 along the inner surface of central lumen 1018. The notchedlayer 1404 includes notches 1402 in any size, shape, arrangement andnumber. Optionally, the notched layer 1404 may include lumens 1406,typically for passage of pullwires 1120. However, the lumens 1406 mayalternatively or in addition be used for other uses. It may also beappreciated that the notched layer 1404 may be incorporated into thewall of the catheter 1000, such as by extrusion, or may be a separatelayer positioned within the catheter 1000. Further, it may beappreciated that the notched layer 1404 may extend the entire length ofthe catheter 1000 or one or more portions of the length of the catheter1000, including simply a small strip at a designated location along thelength of the catheter 1000.

FIG. 54C illustrates a cross-sectional view of the inner guidingcatheter 1020 of FIG. 54A. Here, the catheter 1020 includes protrusions1400 along the outer surface of the catheter 1020. The protrusions 1400may be of any size, shape, arrangement and number. It may be appreciatedthat the protrusions 1400 may be incorporated into the wall of thecatheter 1020, such as by extrusion, may be included in a separatecylindrical layer on the outer surface of the catheter 1020, or theprotrusions 1400 may be individually adhered to the outer surface of thecatheter 1020. Further, it may be appreciated that the protrusions 1400may extend the entire length of the catheter 1000 or one or moreportions of the length of the catheter 1020, including simply a smallstrip at a designated location along the length of the catheter 1020.

Thus, the keying feature may be present along one or more specificportions of the catheters 1000, 1020 or may extend along the entirelength of the catheters 1000, 1020. Likewise, the notches 1402 mayextend along the entire length of the outer guiding catheter 1020 whilethe protrusions 1400 extend along discrete portions of the inner guidingcatheter 1000 and vice versa. It may further be appreciated that theprotrusions 1400 may be present on the inner surface of the outerguiding catheter 1000 while the notches 1402 are present along the outersurface of the inner guiding catheter 1020.

Alternatively or in addition, one or more steerable portions of thecatheter 1000 may comprise a series of articulating members 1180 asillustrated in FIG. 55A. Exemplary embodiments of steerable portions ofcatheters comprising such articulating members 1180 are described inU.S. Pat. No. 7,682,319 (Attorney Docket No. 020489-001210US)incorporated herein by reference for all purposes. FIG. 55B illustratesthe outer guide catheter 1000 having a steerable portion comprisingarticulating members 1180 at its distal end 1016.

Briefly, referring to FIG. 55A, each articulating member 1180 may haveany shape, particularly a shape which allows interfitting or nesting asshown. In addition, it is desired that each member 1180 have thecapability of independently rotating against an adjacent articulatingmember 1180. In this embodiment, the articulating members 1180 compriseinterfitting domed rings 1184. The domed rings 1184 each include a base1188 and a dome 1186. The base 1188 and dome 1186 have a hollow interiorwhich, when the domed rings 1184 are interfit in a series, forms acentral lumen 1190. In addition, the dome 1186 allows each articulatingmember 1180 to mate against an inner surface of an adjacent domed ring1184.

The interfitting domed rings 1184 are connected by at least one pullwire1120. Such pullwires typically extend through the length of the catheter1000 and at least one of the interfitting domed rings 1184 to a fixationpoint where the pullwire 1120 is fixedly attached. By applying tensionto the pullwire 1120, the pullwire 1120 arcs the series of interfittingdomed rings 1184 proximal to the attachment point to form a curve. Thus,pulling or applying tension on at least one pullwire, steers or deflectsthe catheter 1000 in the direction of that pullwire 1120. By positioningvarious pullwires 1120 throughout the circumference of the domed rings1184, the catheter 1000 may be directed in any number of directions.

Also shown in FIG. 55A, each interfitting domed ring 1184 may compriseone or more pullwire lumens 1182 through which the pullwires 1120 arethreaded. Alternatively, the pullwires 1120 may be threaded through thecentral lumen 1190. In any case, the pullwires are attached to thecatheter 1000 at a position where a desired curve is to be formed. Thepullwires 1120 may be fixed in place by any suitable method, such assoldering, gluing, tying, welding or potting, to name a few. Suchfixation method is typically dependent upon the materials used. Thearticulating members 1180 may be comprised of any suitable materialincluding stainless steel, various metals, various polymers orco-polymers. Likewise the pullwires 1120 may be comprised of anysuitable material such as fibers, sutures, metal wires, metal braids, orpolymer braids.

E. Handles

As mentioned previously, manipulation of the guide catheters 1000, 1020is achieved with the use of handles 1056, 1057 attached to the proximalends of the catheters 1000, 1020. FIG. 56 illustrates a preferredembodiment of handles 1056, 1057. As shown, handle 1056 is attached tothe proximal end 1014 of outer guide catheter 1000 and handle 1057 isattached to the proximal end 1024 of inner guide catheter 1020. Innerguide catheter 1020 is inserted through handle 1056 and is positionedcoaxially within outer guide catheter 1000. In this embodiment, thehandles 1056, 1057 are not linked together as shown in the embodimentillustrated in FIG. 48. It may be appreciated that such handles 1056,1057 may alternatively be connected by external connecting rods, bars orplates or by an additional external stabilizing base. An embodiment of astabilizing base will be described in a later section. Referring back toFIG. 56, interventional catheter is inserted through handle 1057 and ispositioned coaxially within inner guide catheter 1020 and outer guidecatheter 1000.

Each handle 1056, 1057 includes two steering knobs 1300 a, 1300 bemerging from a handle housing 1302 for manipulation by a user. Steeringknobs 1300 a are disposed on a side of the housing 1302 and steeringknobs 1300 b are disposed on a face of the housing 1302. However, it maybe appreciated that such placement may vary based on a variety offactors including type of steering mechanism, size and shape of handle,type and arrangement of parts within handle, and ergonomics to name afew.

FIG. 57 illustrates the handles 1056, 1057 of FIG. 56 with a portion ofthe housing 1302 removed to reveal the assemblies of the handles. Eachknob 1300 a, 1300 b controls a steering mechanism which is used to forma curvature in the attached catheter. Each steering mechanism includes ahard stop gear assembly 1304 and a friction assembly 1306. Tension isapplied to one or more pullwires by action of the hard stop gearassembly to form a curve in a catheter. Tension is maintained by thefriction assembly. When tension is released from the one or morepullwires the catheter returns to a straightened position.

FIG. 58 illustrates steering mechanisms within a handle wherein thehousing 1302 is removed for clarity. Here, steering knob 1300 a isattached to a hard stop gear assembly 1304 and a friction assembly (notin view) and steering knob 1300 b is attached to a separate hard stopgear assembly 1304 and friction assembly 1306. Steering knob 1300 a isattached to a knob post 1318 which passes through a base 1308,terminating in a knob gear wheel 1310. The knob gear wheel 1310 actuatesthe hard stop gear assembly 1304, thereby applying tension to one ormore pullwires 1120.

The knob gear wheel 1310 is a toothed wheel that engages a disk gearwheel 1312. Rotation of the steering knob 1300 a rotates the knob post1318 and knob gear wheel 1310 which in turn rotates the disk gear wheel1312. Rotation of the disk gear wheel 1312 applies tension to one ormore pullwires extending through the attached catheter, in this examplethe outer guiding catheter 1000. As shown, the outer guiding catheter1000 passes through the base 1308, wherein one or more pullwires 1120extending through the catheter 1000 are attached to the disk 1314. Suchattachment is schematically illustrated in FIG. 59. Catheter 1000 isshown passing through base 1308. A pullwire 1120 passing through asteering lumen 1162 in the catheter 1000 emerges from the wall of thecatheter 1000, passes through an aperture 1320 in the disk 1314 and isattached to an anchor peg 1316 on the disk 1314. Rotation of the disk1314 (indicated by arrow 1328) around disk post 1315 by action of thedisk gear wheel 1312, applies tension to the pullwire 1120 by drawingthe pullwire 1120 through the aperture 1320 and wrapping the pullwire1120 around the disk 1314 as it rotates. Additional rotation of the disk1314 applies increasing tension to the pullwire 1120. To limit theamount of tension applied to the pullwire 1120, to limit curvature ofthe catheter and/or to avoid possible breakage of the pullwire 1120, therotation of the disk 1314 may be restricted by hard stop peg 1322 whichis attached to the disk 1314 and extends into the base 1308.

FIGS. 60A-60B illustrate how the hard stop peg 1322 is used to restrictrotation of disk 1314. FIGS. 60A-59B provide a top view, wherein thedisk 1314 is disposed on the base 1308. The anchor peg 1316 is shownwith the pullwire 1120 thereattached. A groove 1326 is formed in thebase 1308 beneath the disk 1314 and forms an arc shape. The hard stoppeg 1322 extends from the disk 1314 into the groove 1326 in the base1308. Referring now to FIG. 60B, rotation of the disk 1314 around knobpost 1318, indicated by arrow 1330, draws the pullwire 1120 through theaperture 1320 as previously described, wrapping the pullwire 1120 aroundthe disk 1314. As the disk 1314 rotates, the hard stop peg 1322 followsalong the groove 1326, as shown. The disk 1314 continues rotating untilthe hard stop peg 1322 reaches a hard stop 1324. The hard stop 1324 ispositioned in the groove 1326 and prevents further passage of the hardstop peg 1322. Thus, disk 1314 rotation may be restricted to any degreeof rotation less than or equal to 360 degrees by positioning of the hardstop 1324.

In some instances, it is desired to restrict rotation of the disk 1314to a degree of rotation which is more than 360 degrees. This may beachieved with another embodiment of the hard stop gear assembly 1304.Referring now to FIGS. 61A-61B, a portion of such a hard stop gearassembly 1304 is shown. FIG. 61A illustrates the base 1308 and the diskpost 1315 positioned therethrough. Also shown in the base 1308 is anaperture 1334 through which the knob post 1318, knob gear wheel 1310 andfriction assembly 1306 pass, and a passageway 1336 through which thecatheter 1000 passes. In this embodiment of the hard stop gear assembly1304, a groove 1326 is also present in an arc shape around the disk post1315, however a ball 1332 is positioned in the groove 1326 rather than ahard stop peg 1322. Disk 1314 is positioned over the groove 1326 and theball 1332 as shown in FIG. 61B. The disk 1314, illustrated in FIG. 61C,has a groove 1356 in its surface which is positioned adjacent to thebase 1308, the groove 1356 having an arc shape similar to the groove1326 in the base 1308. The ball 1332 is not fixedly attached to the base1308 or the disk 1314 and is therefore free to move along the channelformed by the groove 1326 in the base 1308 and the groove in the disk1314.

FIGS. 62A-62F illustrate how rotation of the disk 1314 may be restrictedby the ball 1332 to a degree of rotation which is more than 360 degrees.FIGS. 62A-62F illustrate the groove 1326 in the base 1308 wherein thegroove 1326 has an arc shape around disk post 1315. The groove 1326 doesnot form a complete circle; a first groove end 1350 a and a secondgroove end 1350 b form a wall which prevent passage of the ball 1332. Itmay be appreciated that the groove ends 1350 a, 1350 b may be anydistance apart, shortening the length of the groove 1326 by any amount,and allowing the ball 1332 movement, and hence catheter deflection, tobe adjusted to any desired amount. To begin, referring to FIG. 62A, theball 1332 is positioned within the groove 1326 near the first groove end1350 a. The disk 1314 has a matching groove 1352 (shape illustrated indashed line) including a first groove end 1354 a and a second groove end1354 b. The disk 1314 is positioned over the ball 1332 so that the ball1332 is near the second groove end 1354 b.

Referring now to FIG. 62B, the disk 1314 may be rotated while the ball1332 remains in place. Here, the disk 1314 has rotated 90 degrees, asindicated by arrow 36000 and the position of the groove ends 1354 a,1354 b. Referring now to FIG. 62C, the disk 1314 may be further rotatedwhile the ball 1332 remains in place. Here, the disk 1314 has rotated270 degrees, as indicated by arrow 36000 and the position of the grooveends 1354 a, 1354 b. The disk 1314 may continue rotating to 360 degrees,as shown in FIG. 62D, indicated by arrow 36000. Here, the first grooveend 1354 a in the disk 1314 has contacted the ball 1332 and pushes theball 1332 along groove 1326 in the base. Referring now to FIG. 62E, thedisk 1314 may be further rotated while the ball 1332 is pushed along thegroove 1326 in the base 1308 by the first groove end 1354 a in the disk1314. Here, the disk 1314 is shown to have rotated 540 degrees.Referring to FIG. 62F, the disk 1314 rotates until the ball 1332 reachesthe second groove end 1350 b of the base 1308, providing a hard stop. Inthis position, the ball 1332 is held between the first groove end 1354 aof the disk 1314 and the second groove end 1350 b of the base 1308 andfurther rotation of the disk 1314 is prevented. Thus, the disk 1314 wasrotated approximately 660 degrees in this example. Any maximum degree ofrotation may be set by positioning of groove ends 1350 a, 1350 b and/orgroove ends 1354 a, 1354 b. Additionally, in some embodiments, rotationcan be limited by adding more than one ball 1332 to the groove 1326, forexample, two, three, four, five, six, seven, eight, nine, ten or moreballs may be used to limit travel and hence curvature.

It may be appreciated that one or more pullwires 1120 are attached tothe disk 1314 in a manner similar to that illustrated in FIG. 59.Therefore, as the disk 1314 rotates, around disk post 1315 by action ofthe disk gear wheel 1312, tension is applied to the pullwire 1120 bydrawing the pullwire 1120 through the aperture 1320 and wrapping thepullwire 1120 around the disk 1314 as it rotates. Additional rotation ofthe disk 1314 applies increasing tension to the pullwire 1120.Restriction of rotation as described above limits the amount of tensionapplied to the pullwire 1120, to limit curvature of the catheter and/orto avoid possible breakage of the pullwire 1120.

As mentioned, each steering mechanism includes at least a hard stop gearassembly 1304 and a friction assembly 1306. As described above, tensionis applied to one or more pullwires by action of the hard stop gearassembly to form a curve in a catheter. Tension is maintained by thefriction assembly. FIG. 63 illustrates an embodiment of a frictionassembly 1306. The friction assembly 1306 essentially holds a steeringknob, in this example steering knob 1300 b, and the associated knob post1318 in a rotated position. Here, rotation of the knob 1300 b and post1318 rotates attached knob gear wheel 1310. The knob gear wheel 1310actuates the hard stop gear assembly 1304, thereby applying tension toone or more pullwires 1120. The knob gear wheel 1310 is a toothed wheelthat engages a disk gear wheel 1312. Rotation of the steering knob 1300b rotates the knob post 1318 and knob gear wheel 1310 which in turnrotates the disk gear wheel 1312. Rotation of the disk gear wheel 1312applies tension to one or more pullwires extending through the attachedcatheter, in this example the outer guiding catheter 1000.

The steering knob 1300 b and knob post 1318 are held in a rotatedposition by friction provided by a frictional pad 1370. The frictionalpad 1370 is positioned between ring 1372 attached to the knob post 1318and a plate 1374 attached to the base 1308. The knob post 1318 extendsfrom the knob 1300 b through the ring 1372, the frictional pad 1370 andthen the plate 1374. The plate 1374 has internal threads which mate withthreads on the knob post 1318. As the knob post 1318 rotates, thethreads on the post 1318 advance through the threads on the plate 1374.This draws the ring 1372 closer to the plate 1374, compressing thefrictional pad 1370 therebetween. Frictional pad 1370 may be comprisedof any O-ring or sheet material with desirable frictional andcompressibility characteristics, such as silicone rubber, natural rubberor synthetic rubbers, to name a few. In preferred embodiments, an EPDMrubber O-ring is used. Reverse rotation of the knob post 1318 isresisted by friction of the frictional pad 1370 against the ring 1372.The higher the compression of the frictional pad 1370 the stronger thefrictional hold. Therefore, as the steering knob 1300 b is rotated andincreasing amounts of tension are applied to the pullwires 1120,increasing amounts of friction are applied to the ring 1372 to hold theknob 1300 b in place.

Manual reverse rotation of the steering knob 1300 b releases tension onthe pullwires 1120 and draws the ring 1372 away from the plate 1374thereby reducing the frictional load. When tension is released from thepullwires 1120 the catheter 1000 returns toward a straightened position.

It may be appreciated that each handle 1056, 1057 includes a steeringmechanism for each curve to be formed in the attached catheter. Thus, asshown in FIG. 57, handle 1056 includes a steering mechanism to form theprimary curve 1100 in outer guiding catheter 1000 and a steeringmechanism to form the additional curve 1110. Likewise, handle 1057includes a steering mechanism to form the secondary curve 1104 in innerguiding catheter 1020 and a steering mechanism to form the angle theta1070.

Some curves, such as the primary curve 1100, secondary curve 1104 andadditional curve 1110 each typically vary in curvature between astraight configuration and a curved configuration in a single direction.Such movement may be achieved with single set of a hard stop gearassembly 1304 and a friction assembly 1306. However, other curves, suchas the angle theta 1070, may be formed in two directions as shown inFIGS. 49C-49D. Such movement is achieved with two sets of the hard stopgear assembly 1304 and the friction assembly 1306, each set controllingcurvature in a single direction.

FIG. 63 illustrates the presence of an additional set of the frictionassembly 1306′. One or more pullwires 1120′, such as an opposing set asillustrated in FIG. 52D, extending within the wall of the catheter 1000are attached to the disk 1314′ in the same manner as pullwires 1120 areattached to disk 1314. The disks 1314, 1314′ are arranged so thatrotation of steering knob 1300 b in one direction applies tension to thepullwires 1120 via disk 1314 and rotation of steering knob 1300 b in theopposite direction applies tension to the pullwires 1120′ via disk1314′. Likewise, the additional friction assembly 1306′ is shown havinga ring 1372′ attached to the knob post 1318 and a frictional pad 1370′disposed between the ring 1372′ and the opposite side of the plate 1374.Therefore, as rotation of the steering knob 1300 b in the oppositedirection applies tension to the pullwires 1120′ via disk 1314′, thefrictional pad 1370′ applies tension to the ring 1372′ holding the knobpost 1318′ in place.

It may be appreciated that various other mechanisms may be used fortensioning and holding pullwires 1120 in place. Example mechanisms thatmay alternatively be used include clutches, ratchets, levers, knobs,rack and pinions, and deformable handles, to name a few.

F. Interventional System

FIG. 64 illustrates an embodiment of an interventional system 3 of thepresent invention. An embodiment of the multi-catheter guiding system 1of the present invention is shown comprising an outer guide catheter1000, having a proximal end 1014 and a distal end 1016, and an innerguide catheter 1020, having a proximal end 1024 and a distal end 1026,wherein the inner guide catheter 1020 is positioned coaxially within theouter guide catheter 1000, as shown. In addition, a hemostatic valve1090 is disposed within handle 1056 or external to handle 1056 as shownto provide leak-free sealing with or without the inner guide catheter1020 in place. The valve 1090 also prevents back bleeding and reducesthe possibility of air introduction when inserting the inner guidecatheter 1020 through the outer guide catheter 1000. An example of ahemostatic valve 1090 is illustrated in FIG. 64A, however any suitablevalve or hemostatic valve may be used to provide similar functions. InFIG. 64A, the valve 1090 has a first end 1091, a second end 1092 and alumen 1093 therethrough. The inner wall of lumen 1093 is preferablytapered toward end 1091 and may further include a plurality of taperedaxial channels configured to receive the protrusions 1400 on the innerguide catheter 1020. The first end 1091 is attached to the outer guidecatheter 1000 and the second end 1092 is free. Referring now back toFIG. 64, the distal ends 1016, 1026 of catheters 1000, 1020,respectively, are sized to be passable to a body cavity, typicallythrough a body lumen such as a vascular lumen.

To assist in inserting the fixation device 14 through a hemostatic valve1090, a fixation device introducer may be used. For example, when thefixation device 14 is loaded on a delivery catheter 300 and an innerguide catheter 1020, insertion of the fixation device 14, deliverycatheter 300 and inner guide catheter 1020 through an outer guidecatheter 1000 involves passing the fixation device 14 through ahemostatic valve 1090 on the outer guide catheter 1000. To reduce anytrauma to the fixation device 14 by the hemostatic valve 1090, afixation device introducer may be used. An embodiment of a fixationdevice introducer 1420 is illustrated in FIG. 64B. The introducer 1420includes a loading body 1422 and an insertion endpiece 1424. Thefixation device 14 is loaded into the loading body 1422 and into theinsertion endpiece 1424 to approximately the dashed line 1428. Theinsertion endpiece 1424 has a split end creating individual splitsections 1430, in this embodiment, four split sections 1430. Bycompressing the split sections 1430, the endpiece 1424 forms a taper.Such a taper is then inserted through a hemostatic valve 1090, so thatthe insertion endpiece 1424 creates a smooth passageway through thevalve for the fixation device 14. Once the insertion endpiece 1424 isinserted through the valve 1090, the fixation device 14, and attacheddelivery catheter 300 and inner guide catheter 1020, may then beadvanced through the fixation device introducer 1420. The fixationdevice introducer 1420 also includes a hemostatic valve within theloading body 1422 to prevent any backbleeding or leakage through theintroducer 1420.

Manipulation of the guide catheters 1000, 1020 is achieved with the useof handles 1056, 1057 attached to the proximal ends of the catheters1000, 1020. As shown, handle 1056 is attached to the proximal end 1014of outer guide catheter 1000 and handle 1057 is attached to the proximalend 1024 of inner guide catheter 1020. Inner guide catheter 1020 isinserted through handle 1056 and is positioned coaxially within outerguide catheter 1000.

An embodiment of the delivery catheter 300 of the present invention isinserted through handle 1057 and is positioned coaxially within innerguide catheter 1020 and outer guide catheter 1000. Therefore, ahemostatic valve 1090 is disposed within handle 1057 or external tohandle 1057 as shown to provide leak-free sealing with or without thedelivery catheter 300 in place. The valve 1090 functions as describedabove. The delivery catheter 300 includes a shaft 302, having a proximalend 322 and a distal end 324, and a handle 304 attached to the proximalend 322. A fixation device 14 is removably coupled to the distal end 324for delivery to a site within the body.

The outer guide catheter 1000 and/or the inner guide catheter 1020 areprecurved and/or have steering mechanisms to position the distal ends1016, 1026 in desired directions. Precurvature or steering of the outerguide catheter 1000 directs the distal end 1016 in a first direction tocreate a primary curve while precurvature and/or steering of the innerguide catheter 1020 directs distal end 1026 in a second direction,differing from the first, to create a secondary curve. Together, theprimary and secondary curves form a compound curve. Advancement of thedelivery catheter 300 through the coaxial guide catheters 1000, 1020guides the delivery catheter 300 through the compound curve toward adesired direction, usually in a direction which will position thefixation device 14 in a desired location within the body.

FIG. 65 illustrates portions of another embodiment of an interventionalsystem 3 of the present invention. Handles 1056, 1057 of themulti-catheter guiding system 1 of the present invention are shown. Eachhandle 1056, 1057 includes a set of steering knobs 1300 a, 1300 b, asshown. Manipulation of the guide catheters 1000, 1020 is achieved withthe use of the steering knobs 1300 a, 1300 b attached to the proximalends of the catheters 1000, 1020. Handle 304 of the delivery catheter300 is also shown, including the proximal element line handle 312, thelock line handle 310, the actuator rod control 314 and the actuator rodhandle 316, among other features. The handle 304 is supported by thesupport base 306 which is connected to the handle 1057.

It may be appreciated the above described systems 3 are not intended tolimit the scope of the present invention. The systems 3 may include anyor all of the components of the described invention. In addition, themulti-catheter guiding system 1 of the present invention may be used tointroduce other delivery catheters, interventional catheters or otherdevices. Likewise, the delivery catheter 300 may be introduced throughother introducers or guiding systems. Also, the delivery catheter 300may be used to deliver other types of devices to a target locationwithin the body, including endoscopic staplers, devices forelectrophysiology mapping or ablation, septal defect repair devices,heart valves, annuloplasty rings and others.

In addition, many of the components of the system 3 may include one ormore hydrophilic coatings. Hydrophilic coatings become slippery whenwet, eliminate the need for separate lubricants. Thus, such coatings maybe present on the multi-catheter guiding system, delivery catheter, andfixation device, including the proximal elements and distal elements, toname a few.

Further, the system 3 may be supported by an external stabilizer base1440, an embodiment of which is illustrated in FIG. 66. Stabilizer base1440 maintains the relative positions of the outer guide, inner guideand delivery catheter during a procedure. In this embodiment, the base1440 comprises a platform 1442 having a planar shape for positioning onor against a flat surface, such as a table or benchtop. The base 1440further includes a pair of handle holders 1444, 1448, each attached tothe platform 1442 and extending upwardly from the platform 1442, eitherangularly or perpendicularly. Handle holder 1444 includes a notch 1446for holding the outer guiding catheter 1000, as illustrated in FIG. 67,thereby supporting the handle 1056. FIG. 67 shows the handle 1056attached to the outer guiding catheter 1000 positioned so that theproximal end 1014 of the outer guiding catheter 1000 rests in the notch1446. Referring back to FIG. 66, handle holder 1448 includes an elongateportion 1452 having a trough 1450 and a hooked end 1454. As shown inFIG. 68, handle 1057 rests on the elongate portion 1452 and the handle304 rests on hooked end 1454 so that the inner guiding catheter 1020extends from the handle 1057 to the handle 1056 and continues on withinouter guiding catheter 1000. The handle 304 is additionally supported bysupport base 306, as shown.

It may be appreciated that the stabilizer base 1440 may take a varietyof forms and may include differences in structural design to accommodatevarious types, shapes, arrangements and numbers of handles.

G. Kits

Referring now to FIG. 69, kits 1500 according to the present inventioncomprise any of the components described in relation to the presentinvention. The kits 1500 may include any of the components describedabove, such as the outer guide catheter 1000 including handle 1056, theinner guide catheter 1020 including handle 1057, the delivery catheter300 and the fixation device 14 and instructions for use IFU. Optionally,any of the kits may further include any other system componentsdescribed above, such as various interventional tools 1040, orcomponents associated with positioning a device in a body lumen, such asa guidewire 1202, dilator 1206 or needle 1204. The instructions for useIFU will set forth any of the methods as described above, and all kitcomponents will usually be packaged together in a pouch 1505 or otherconventional medical device packaging. Usually, those kit componentswhich will be used in performing the procedure on the patient will besterilized and maintained within the kit. Optionally, separate pouches,bags, trays or other packaging may be provided within a larger package,where the smaller packs may be opened separately to separately maintainthe components in a sterile fashion.

While the foregoing is a complete description of the preferredembodiments of the invention, various alternatives, substitutions,additions, modifications, and equivalents are possible without departingfrom the scope of the invention. For example, in many of theabove-described embodiments, the invention is described in the contextof approaching a valve structure from the upstream side—that is, theatrial side in the case of a mitral valve. It should be understood thatany of the foregoing embodiments may be utilized in other approaches aswell, including from the ventricular or downstream side of the valve, aswell as using surgical approaches through a wall of the heart. Moreover,the invention may be used in the treatment of a variety of other tissuestructures besides heart valves, and will find usefulness in a varietyof tissue approximation, attachment, closure, clamping and ligationapplications, some endovascular, some endoscopic, and some opensurgical.

Again, although the foregoing invention has been described in somedetail by way of illustration and example, for purposes of clarity ofunderstanding, it will be obvious that various alternatives,modifications and equivalents may be used and the above descriptionshould not be taken as limiting in scope of the invention which isdefined by the appended claims.

1. A system for fixing tissue, said system comprising: an implantabletissue fixation device comprising a pair of fixation elements eachhaving a first end, a free end opposite the first end, and an engagementsurface therebetween for engaging the tissue, the fixation devicefurther comprising a pair of gripping elements, each gripping elementmoveable with respect to one of the fixation elements and being disposedin opposition to one of the engagement surfaces so as to capture tissuetherebetween; and a gripper pusher releasably coupled to the implantablefixation device adjacent the pair of gripping elements, the gripperpusher having an expanded configuration and a collapsed configuration,wherein in the expanded configuration the gripper pusher engages thepair of gripping elements and advances the pair of gripping elementstoward the engagement surfaces of the fixation elements, and wherein inthe collapsed configuration the gripper pusher has a reduced radialprofile relative to the gripper pusher radial profile in the expandedconfiguration thereby allowing the pair of gripping elements to moveaway from the engagement surfaces of the fixation elements.
 2. Thesystem of claim 1, wherein the first ends are movably coupled togethersuch that the fixation elements are moveable between a closed positionwherein the engagement surfaces face each other to an inverted positionwherein the engagement surfaces face away from each other.
 3. The systemof claim 1, wherein each fixation element is at least partially concavesuch that each gripping element is separated from an opposing engagementsurface in an undeployed configuration, and each gripping element is atleast partially recessed within the fixation element in a deployedconfiguration.
 4. The system of claim 2, wherein the fixation elementsare further moveable to an open position between the closed position andthe inverted position.
 5. The system of claim 1, wherein the grippingelements are movable independently of the fixation elements.
 6. Thesystem of claim 1, wherein the gripping elements are biased toward theengagement surfaces.
 7. The system of claim 1, wherein the grippingelements are approximately parallel to each other in an undeployedconfiguration.
 8. The system of claim 1, wherein the gripper pushercomprises a spring element that moves from the collapsed configurationto the expanded configuration when a compressive force is appliedthereto.
 9. The system of claim 8, wherein the spring element comprisesa longitudinal axis, and the compressive force is applied in a directionsubstantially parallel thereto.
 10. The system of claim 8, wherein thespring element is resiliently biased to return to the collapsedconfiguration when the compressive force is released.
 11. The system ofclaim 8, wherein the gripper pusher comprises two spring elements. 12.The system of claim 1, wherein the gripper pusher comprises an elongatedeflectable arm.
 13. The system of claim 12, wherein the deflectable armis biased to return to the expanded configuration.
 14. The system ofclaim 13, wherein proximal retraction of the proximal elements collapsesthe deflectable arm from the expanded configuration to the collapsedconfiguration.
 15. The system of claim 12, wherein the arm comprises aplurality of peaks.
 16. The system of claim 1, wherein the gripperpusher comprises an attachment mechanism for releasably attaching adistal portion of the gripper pusher to the implantable fixation device.17. The system of claim 16, wherein the attachment mechanism comprises anotched region on the distal portion of the gripper pusher, and a bossadjacent a proximal end of the implantable fixation device, wherein thenotched region is sized to accept the boss.
 18. The system of claim 1,further comprising an elongate delivery shaft having a proximal portionand a distal portion, wherein the distal portion of the elongatedelivery shaft is releasably coupled to a proximal portion of thegripper pusher.
 19. The system of claim 18, wherein the gripper pushercomprises an attachment ring coupled to the proximal portion thereof,the attachment ring slidably disposed over the delivery shaft.
 20. Thesystem of claim 2, further comprising an actuation mechanism coupled tothe fixation elements adapted to move the fixation elements between theclosed position and the inverted position.
 21. The system of claim 1,further comprising a coupling member for detachably coupling thefixation device to an elongate delivery shaft.
 22. The system of claim1, further comprising a covering on the fixation elements adapted forpromoting tissue growth.
 23. The system of claim 1, further comprising acoating on the fixation elements adapted for delivering a therapeuticagent.
 24. A system for fixing tissue, said system comprising: animplantable tissue fixation device comprising a pair of fixationelements, the pair of fixation elements comprising a first fixationelement and a second fixation element, each fixation element having afirst end, a free end opposite the first end, and an engagement surfacetherebetween for engaging the tissue, the fixation device furthercomprising a pair of gripping elements, the pair of gripping elementscomprising a first gripping element and a second gripping element, thefirst gripping element moveable with respect to the first fixationelement and being disposed in opposition to the engagement surface ofthe first fixation element so as to capture tissue therebetween, and thesecond gripping element moveable with respect to the second fixationelement and being disposed in opposition to the engagement surface ofthe second fixation element so as to capture tissue therebetween; and afirst gripper actuator releaseably coupled to the implantable fixationdevice adjacent to the first gripping element, the first gripperactuator having a first configuration and a second configuration,wherein actuating the first gripper actuator between the firstconfiguration and the second configuration moves the first grippingelement with respect to the first fixation element.
 25. The system ofclaim 24, further comprising a second gripper actuator releaseablycoupled to the implantable fixation device adjacent to the secondgripping element, the second gripper actuator having a firstconfiguration and a second configuration, wherein acutating the secondgripper actuator between the first configuration and the secondconfiguration moves the second gripping element with respect to thesecond fixation element.
 26. The system of claim 25, wherein the firstgripper actuator and the second gripper actuator are actuatable betweenthe first configurations and the second configurations independently ofeach other.
 27. The system of claim 24, wherein the first ends aremovably coupled together such that the fixation elements are moveablebetween a closed position wherein the engagement surfaces face eachother and an inverted position wherein the engagement surfaces face awayfrom each other.
 28. The system of claim 27, further comprising anactuation mechanism coupled to the fixation elements adapted to move thefixation elements between the closed position and the inverted position.29. The system of claim 24, wherein each fixation element is at leastpartially concave such that each gripping element is separated from anopposing engagement surface in an undeployed configuration, and eachgripping element is at least partially recessed within the fixationelement in a deployed configuration.
 30. The system of claim 29, whereinthe fixation elements are further moveable to an open position betweenthe closed position and the inverted position.
 31. The system of claim24, wherein the gripping elements are movable independently of thefixation elements.
 32. The system of claim 24, wherein the grippingelements are biased toward the engagement surfaces.
 33. The system ofclaim 24, wherein the gripping elements are substantially parallel toeach other in an undeployed configuration.
 34. The system of claim 24,further comprising a gripper pusher releasably coupled to theimplantable fixation device adjacent the pair of gripping elements, thegripper pusher having an expanded configuration and a collapsedconfiguration, wherein in the expanded configuration the gripper pusherengages one or more of the pair of gripping elements and advances one ormore of the pair of gripping elements toward the engagement surfaces ofthe fixation elements, and wherein in the collapsed configuration thegripper pusher has a reduced radial profile relative to the gripperpusher radial profile in the expanded configuration thereby allowing thepair of gripping elements to move away from the engagement surfaces ofthe fixation elements.
 35. The system of claim 26, wherein the firstgripper actuator comprises a first wire and second gripper actuatorcomprises a second wire.
 36. The system of claim 35, wherein the firstwire and the second wire are substantially flat.
 37. The system of claim36, wherein a substantially flat side of the first wire is positioned toengage the first gripping element and a substantially flat side of thesecond wire is positioned to engage the second gripping element.
 38. Thesystem of claim 37, wherein the first wire is biased to bend along thesubstantially flat side of the first wire and wherein the second wire isbiased to bend along the substantially flat side of the second wire. 39.The system of claim 26, wherein at least one of a distal end of thefirst gripper actuator or a distal end of the second gripper actuator isreleaseably coupled to the implantation fixation device by a sutureknot.
 40. The system of claim 26, further comprising an elongatedelivery shaft having a proximal portion and a distal portion, whereinthe distal portion of the elongate delivery shaft is releasably coupledto a proximal portion of the fixation device.
 41. The system of claim40, wherein the first gripper actuator comprises a distal portion andthe second gripper actuator comprises a distal portion, wherein thedistal portions of the first gripper actuator and second gripperactuator are releasably coupled to at least one of the distal portion ofthe elongate delivery shaft or the proximal portion of the fixationdevice.
 42. The system of claim 41, wherein the distal portions of thefirst gripper actuator and second gripper actuator each comprise aclosed loop.
 43. The system of claim 41, wherein the distal portions ofthe first gripper actuator and second gripper actuator each comprise aclosed loop a coiled distal end.
 44. The system of claim 40, wherein theproximal portion of the fixation device comprises a channel having apair of notches, wherein the distal portion of the elongate deliveryshaft comprises a pair of L-shaped ends resiliently biased to fit intothe pair of notches, and wherein the distal portion of the elongatedelivery shaft is releasably coupled to the proximal portion of thefixation device by placing the pair of L-shaped ends into channel of thefixation device and locking the pair of notches in the channel.
 45. Thesystem of claim 44, wherein the first gripper actuator and the secondgripper actuator each comprise distal ends, and wherein placing thedistal ends of the first gripper actuator and the second gripperactuator and coupling the distal portion of the elongate delivery shaftto the proximal portion of the fixation device locks the distal ends ofthe first gripper actuator and the second gripper actuator in place. 46.The system of claim 44, wherein the first gripper actuator and thesecond gripper actuator each comprise T-shaped distal ends.
 47. Thesystem of claim 46, further comprising a covering assembly coupled toand disposed over the distal portion of the elongate delivery shaft, thecovering assembly comprising an outer slideable section and an innersection having a pair of T-shaped openings, wherein the first gripperactuator and second gripper actuator are releaseably coupled to thefixation device by sliding the T-shaped distal ends of the first gripperactuator and second gripper actuator into the pair of the T-shapedopening of the inner section of the covering assembly and sliding theouter slideable section to cover the T-shaped openings.
 48. The systemof claim 26, wherein the first gripper actuator is releaseably coupledto the first gripping element and the second gripper actuator isreleaseable coupled to the second gripping element.
 49. The system ofclaim 48, wherein the first gripping element and the second grippingelement each comprise portions extending radially outward.
 50. Thesystem of claim 49, further comprising a first holding element and asecond holding element, wherein the first holding element is coupled tothe first gripper actuator and releaseably coupled to the first grippingelement at the portion extending radially outward of the first grippingelement, and wherein the second holding element is coupled to the secondgripper actuator and releaseably coupled to the second gripping elementat the portion extending radially outward of the second grippingelement.
 51. The system of claim 50, wherein the first holding elementcomprises a first ring disposed over the portion extending radiallyoutward of the first gripping element, and the second holding elementcomprises a second ring disposed over the portion extending radiallyoutward of the second gripping element.
 52. The system of claim 50,wherein the first holding element comprises a first clip releaseablyattached to the portion extending radially outward of the first grippingelement, and wherein the second holding element comprises a second clipreleaseably attached to the portion extending radially outward of thesecond gripping element.
 53. The system of claim 52, wherein the firstclip comprises a pair of first clip legs disposed over length of thefirst gripping element, and the second clip comprises a pair of secondclip legs disposed over length of the second gripping element.
 54. Thesystem of claim 49, wherein the portions extending radially outward ofthe first gripping element and the second gripping element each haveapertures, wherein the first gripper actuator is threaded through theaperture of the portion extending radially outward of the first grippingelement, and wherein the second gripper actuator is threaded through theaperture of the portion extending radially outward of the secondgripping element.
 55. The system of claim 54, wherein the first gripperactuator and the second gripper actuator each comprise an enlargedportion, wherein a diameter of the enlarged portions of the firstgripper actuator may be greater than the diameter of the aperture of theportion extending radially outward of the first gripping element tofacilitate moving the first gripping element, and wherein a diameter ofthe enlarged portions of the second gripper actuator may be greater thanthe diameter of the aperture of the portion extending radially outwardof the second gripping element to facilitate moving the second grippingelement.
 56. The system of claim 55, wherein the enlarged portion of thefirst gripper actuator comprises a sleeve disposed over the firstgripper mover and the englarged portion of the second gripper actuatorcomprises a sleeve disposed over the second gripper mover.
 57. Thesystem of claim 26, wherein the first gripper actuator and the secondgripper actuator each comprise an actuation line and a release line. 58.The system of claim 57, wherein the actuation line of the first gripperactuator comprises a loop and the release line of the first gripperactuator comprises a single release cable threaded through the loop ofthe actuation line when the first gripper actuator is coupled to thefirst gripping element, and wherein the actuation line of the secondgripper actuator comprises a loop and the release line of the secondgripper actuator consists essentially of a single release cable threadedthrough the loop of the actuation line when the second gripper actuatoris coupled to the second gripping element.
 59. The system of claim 58,wherein pulling the single release cable of the first gripper actuatorout through the loop of the actuation line of the first gripper actuatorallows the first gripper actuator to be released from the first grippingelement, and wherein pulling the single release cable of the secondgripper actuator out through the loop of the actuation line of thesecond gripper actuator allows the first gripper actuator to be releasedfrom the second gripping element.
 60. The system of claim 24, furthercomprising a coupling member for detachably coupling the fixation deviceto an elongate delivery shaft.
 61. The system of claim 24, furthercomprising a covering on the fixation elements adapted for promotingtissue growth.
 62. The system of claim 24, further comprising a coatingon the fixation elements adapted for delivering a therapeutic agent. 63.A method for fixing tissue, said method comprising: providing animplantable tissue fixation device comprising a pair of fixationelements each having a first end, a free end opposite the first end, andan engagement surface therebetween for engaging the tissue, the fixationdevice further comprising a pair of gripping elements, each grippingelement moveable with respect to one of the fixation elements and beingdisposed in opposition to one of the engagement surfaces so as tocapture tissue therebetween; positioning the fixation element relativeto tissue so that the tissue is disposed between the pair of grippingelements and the engagement surfaces of the pair of fixation element;actuating a gripper actuation element to engage and displace one or moreof the gripping elements; and advancing the pair of gripping elementstoward the engagement surfaces of the fixation elements.
 64. The methodof claim 63, further comprising: providing a gripper pusher releasablycoupled to the implantable fixation device adjacent the pair of grippingelements; and wherein advancing the pair of gripping elements toward theengagement surfaces of the fixation elements comprises engaging the pairof gripping elements with the gripper pusher.
 65. The method of claim64, wherein engaging the pair of gripping elements with the gripperpusher comprises placing the gripper pusher into an expandedconfiguration from a collapsed configuration.
 66. The method of claim65, wherein the gripper pusher comprises a spring element having alongitudinal axis, and wherein engaging the pair of gripping elementswith the gripper pusher comprises applying a compressive force to thespring element in a direction substantially parallel to the longitudinalaxis to move the gripper pusher to the expanded configuration.
 67. Themethod of claim 65, further comprising placing the gripper pusher intothe collapsed configuration from the expanded configuration to reducethe radial profile of the gripper pusher relative to the gripper pusherradial profile in the expanded configuration to allow the pair ofgripping elements to move away from the engagement surfaces of thefixation elements.
 68. The method of claim 63, further comprising movingthe first ends of the pair of the fixation elements between a closedposition wherein the engagement surface face each other to an invertedposition wherein the engagement surfaces face away from each other. 69.The method of claim 68, further comprising moving fixation elements toan open position between the closed position and the inverted position.70. A method of fixing tissue, said method comprising: providing animplantable tissue fixation device, the fixation device comprising apair of fixation elements, the pair of fixation elements comprising afirst fixation element and a second fixation element, each fixationelement having a first end, a free end opposite the first end, and anengagement surface therebetween for engaging the tissue, the fixationdevice further comprising a pair of gripping elements, the pair ofgripping elements comprising a first gripping element and a secondgripping element, the first gripping element being disposed inopposition to the engagement surface of the first fixation element andthe second gripping element being disposed in opposition to theengagement surface of the second fixation element; positioning thefixation element relative to tissue so that the tissue is disposedbetween the first gripping element and the engagement surface of thefirst fixation element; capturing the tissue between the first grippingelement and the engagement surface of the first fixation element bymoving the first gripping element with respect to the first fixationelement, and maintaining the position of the second gripping elementwith respect to the second fixation element while the first grippingelement is moved with respect to the first fixation element.
 71. Themethod of claim 70, further comprising providing a first grippingelement actuator coupled to the first gripping element and providing asecond gripping element actuator coupled to the second gripping element,wherein capturing the tissue between the first gripping element and theengagement surface of the first fixation element comprises moving thefirst gripping element actuator to move the first gripping element; andmaintaining the position of the second gripping element with respect tothe second fixation element comprises holding the second grippingelement actuator stationary relative to the second gripping element. 72.The method of claim 70, further comprising releasing the captured tissuebetween the first gripping element and the engagement surface of thefirst fixation element by moving the first gripping element away fromthe first fixation element.
 73. The method of claim 72, furthercomprising repositioning the fixation element relative to the tissue.74. The method of claim 70, further comprising positioning the fixationelement relative to tissue so that the tissue is disposed between thesecond gripping element and the engagement surface of the secondfixation element; and capturing the tissue between the second grippingelement and the engagement surface of the second fixation element bymoving the second gripping element with respect to the second fixationelement.
 75. The method of claim 74, further comprising releasing thecaptured tissue between the first gripping element and the engagementsurface of the first fixation element by moving the first grippingelement away from the first fixation element; and releasing the capturedtissue between the second gripping element and the engagement surface ofthe second fixation element by moving the second gripping element awayfrom the second fixation element.
 76. The method of claim 75, furthercomprising repositioning the fixation element relative to the tissue.77. A system for fixing tissue, said system comprising: an implantabletissue fixation device comprising a pair of fixation elements, the pairof fixation elements comprising a first fixation element and a secondfixation element, each fixation element having a first end, a free endopposite the first end, and an engagement surface therebetween forengaging the tissue, the fixation device further comprising a pair ofgripping elements, the pair of gripping elements comprising a firstgripping element and a second gripping element, the first grippingelement moveable with respect to the first fixation element and beingdisposed in opposition to the engagement surface of the first fixationelement so as to capture tissue therebetween, and the second grippingelement moveable with respect to the second fixation element and beingdisposed in opposition to the engagement surface of the second fixationelement so as to capture tissue therebetween; a first gripper actuatorreleaseably coupled to the implantable fixation device adjacent to thefirst gripping element, the first gripper actuator having a firstconfiguration and a second configuration, wherein actuating the firstgripper actuator between the first configuration and the secondconfiguration moves the first gripping element with respect to the firstfixation element; a gripper pusher releasably coupled to the implantablefixation device adjacent the pair of gripping elements, the gripperpusher having an expanded configuration and a collapsed configuration,wherein in the expanded configuration the gripper pusher engages one ormore of the pair of gripping elements and advances one or more of thepair of gripping elements toward the engagement surfaces of the fixationelements, and wherein in the collapsed configuration the gripper pusherhas a reduced radial profile relative to the gripper pusher radialprofile in the expanded configuration thereby allowing the pair ofgripping elements to move away from the engagement surfaces of thefixation elements; a delivery catheter for delivering the implantablefixation device; and a handle configured to actuate the pair of fixationelements, the first gripper actuator and the gripper pushersimultaneously.
 78. The system according to claim 77, wherein the handlecomprises an actuator rod actuator for actuating the pair of fixationelements; a first gripper actuator handle for actuating the firstgripper actuator; a pusher attachment connected to the first gripperactuator handle to actuate the gripper pusher; and a gripper pusherretraction wire configured to couple a retraction of the first gripperactuator and the pusher attachment with the actuating of the pair offixation elements.
 79. The system according to claim 78, wherein thehandle is further configured to retract the first gripper actuator andthe first gripper actuator handle when the actuator rod actuator isactuated to reduce the angle between the pair of fixation elements. 80.The system according to claim 79, wherein the pusher attachment isconnected to the first gripper actuator handle using a spring to enablea different amount of displacement between the gripper pusher and thefirst gripping element.